Paralytic poliomyelitis in Russian Federation in 1998-2005

From 1998 through 2005 3,294 cases of acute flaccid paralysis (AFP) including 93 cases with clinical picture of poliomyelitis were registered in Russian Federation. From the latter cases 91 were classified as vaccine-associated paralytic poliomyelitis (VAPP): 66 were VAPP cases in oral poliomyelitis vaccine (OPV) recipients and 25--VAPP cases in contacts. VAPP rate was 1 case per 1.6 million of distributed OPV doses, 1 case per 2.2 million doses for OPV recipients, and 1 case per 186,000 doses for recipients of 1st OPV dose in children aged < 1 year. Majority of VAPP cases in recipients occurred after 1st dose (89.4%) and in contacts--in non-vaccinated children (76%). Mean interval between OPV administration and onset of VAPP in recipients was 21 days. Children aged < 1 year were predominant among VAPP cases (92.4% among recipient VAPP cases, and 80% among contact VAPP cases). Majority of the patients had unfavorable health status including defects of immunity. Most of poliovirus strains isolated from VAPP cases belonged to type 3 (52.9%) whereas to type 2 and 1--29.8% and 17.4% of strains respectively. All VAPP cases were associated with vaccine-derived polioviruses. A highly diverged poliovirus type 1 (2.65% of nucleotide substitutions in VP1 region) was isolated from patient with contact VAPP. Formation of poliovirus-neutralizing serum antibodies in children with VAPP including persons with immunodeficiency reflects the ability of the organism to produce specific antiviral immune response.     

泰安市维持无脊髓灰质炎状态的策略与效果分析

目的调查泰安市保持无脊髓灰质炎(简称无脊灰)状态所采取的策略和取得的效果,为证实无脊灰提供依据,并为其他疫苗针对传染病的控制与消除提供借鉴。方法采用描述流行病学研究方法,对该市2001—2011年保持无脊灰状态所采取的策略和效果进行回顾性分析。结果证实泰安市2001年实现无脊灰以来,始终正确地实施脊髓灰质炎疫苗免疫策略,加强对急性弛缓性麻痹病例监测,完善免疫规划科学管理,巩固了自1991年5月以来无脊髓灰质炎野病毒感染病例发生的成果。结论持续做好免疫、监测、管理三大策略对维持无脊髓灰质炎状态至关重要,并为其他疫苗针对疾病的控制提供了理论借鉴。     

Poliomyelitis and vaccination strategy in Russian Federation in post-certification period

Immunization schedules implemented in various countries by using poliovirus vaccines are presented. Approaches to prevent development of vaccine associated paralytic poliomyelitis and risk groups for this infection are discussed. In recent years poliomyelitis morbidity situation in the European region has become more complex, with the example of poliomyelitis outbreak in Tajikistan in 2010. The resulting problem of protection of Russian against emergence and spread of poliomyelitis caused by wild type virus is discussed.     

A statistical model of the international spread of wild poliovirus in Africa used to predict and prevent outbreaks

Background

Outbreaks of poliomyelitis in African countries that were previously free of wild-type poliovirus cost the Global Polio Eradication Initiative US$850 million during 2003–2009, and have limited the ability of the program to focus on endemic countries. A quantitative understanding of the factors that predict the distribution and timing of outbreaks will enable their prevention and facilitate the completion of global eradication.

Methods and Findings

Children with poliomyelitis in Africa from 1 January 2003 to 31 December 2010 were identified through routine surveillance of cases of acute flaccid paralysis, and separate outbreaks associated with importation of wild-type poliovirus were defined using the genetic relatedness of these viruses in the VP1/2A region. Potential explanatory variables were examined for their association with the number, size, and duration of poliomyelitis outbreaks in 6-mo periods using multivariable regression analysis. The predictive ability of 6-mo-ahead forecasts of poliomyelitis outbreaks in each country based on the regression model was assessed. A total of 142 genetically distinct outbreaks of poliomyelitis were recorded in 25 African countries, resulting in 1–228 cases (median of two cases). The estimated number of people arriving from infected countries and <5-y childhood mortality were independently associated with the number of outbreaks. Immunisation coverage based on the reported vaccination history of children with non-polio acute flaccid paralysis was associated with the duration and size of each outbreak, as well as the number of outbreaks. Six-month-ahead forecasts of the number of outbreaks in a country or region changed over time and had a predictive ability of 82%.

Conclusions

Outbreaks of poliomyelitis resulted primarily from continued transmission in Nigeria and the poor immunisation status of populations in neighbouring countries. From 1 January 2010 to 30 June 2011, reduced transmission in Nigeria and increased incidence in reinfected countries in west and central Africa have changed the geographical risk of polio outbreaks, and will require careful immunisation planning to limit onward spread. Please see later in the article for the Editors'' Summary     

A RT-PCR method for selective amplification and phenotypic characterization of all three serotypes of Sabin-related polioviruses from viral mixtures

Outbreaks caused by vaccine-derived polioviruses are challenging the final eradication of paralytic poliomyelitis. Therefore, the surveillance of the acute flaccid paralysis cases based on poliovirus isolation and characterization remains an essential activity. Due to the use of trivalent oral poliovirus vaccine (OPV), mixtures containing more than one serotype of Sabin-related polioviruses are frequently isolated from clinical samples. Because each poliovirus isolate needs to be individually analyzed, we designed polymerase chain reaction primers that can selectively distinguish and amplify a genomic segment of the three Sabin-related poliovirus serotypes present in mixtures, thus, optimizing the diagnosis and providing prompt information to support epidemiologic actions.     

Outbreaks of paralytic poliomyelitis and polio surveillance in Shandong province of China.

Widespread outbreaks of paralytic poliomyelitis occurred in Shandong province, China, starting from 1988. In 1989, 484 cases were recorded, which was the peak during the past 4 years. Although emergency immunization with trivalent oral poliovirus vaccine (OPV) was carried out in selected counties in 1989 and 1990, control of the outbreak was not satisfactory. OPV mass immunization campaigns were introduced to cover the whole province in early 1991, and the number of patients with paralytic poliomyelitis decreased to 95. In addition to this new immunization strategy, we began to construct new polio surveillance systems. These were a network for case-negative reporting and an immediate reporting system of acute flaccid paralysis (AFP). As for the case-negative reporting, presently more than 90% of counties have been reporting presence or absence of new AFP cases. Monitoring of AFP immediate reporting has also shown a gradual improvement in several aspects. These polio surveillance activities are crucial to polio eradication programme management.     

Surveillance of acute flaccid paralysis in Belarus

The ten-years experience of acute flaccid paralysis (AFP) surveillance in Belarus has been summarized. Among 456 AFP cases reported from 1996 to 2005, 11 were classified as vaccine-associated paralytic poliomyelitis (VAPP), 445--as non-polio AFP. The risk of VAPP for the period 1996-2001 was 1 case per 745,000 used doses of oral poliovaccine (OPV). For the recipients of OPV the risk was 1 case per 911,700 doses and for the first-dose recipients--1 case per 96,000 doses. The high incidence of VAPP was a reason for implementation of sequential polio vaccination schedule in 2000. Guillain-Barre syndrome dominated among non-polio AFP (39.3% of cases); more rare were traumatic neuritis (27.9% of cases), transient monoparalysis (12.1%), myelitis (7.6%). Non-polio AFP differed from VAPP by following epidemiological and virological characteristics: predominance of previously repeatedly vaccinated against poliomyelitis; development of paralysis in long-term period after vaccination; isolation of non-polio viruses belonged to three serotypes of Coxsackie B viruses (B1, B4, B6) and six serotypes of Echo viruses (6, 7, 11, 14, 24, 25) in 8.1% of cases; absence of typical for polio residual paralyses in patients who excreted vaccine polioviruses.     

The maintaining of the active laboratory-based surveillance of the acute flaccid paralysis (AFP) cases in Romania in the framework of the strategic plan of the global polio eradication initiative

Until 2008 poliomyelitis was controlled in Romania by predominantly using Oral Poliovirus Vaccine Sabin (OPV); the alternative vaccination schedule (IPV formalin Inactivated Poliovirus Vaccine/OPV) will be implemented starting September 2008. The vaccination coverage with 4 doses of TOPV (trivalent oral polio vaccine) in the first 14 months of life has been > 90% since 1980. In Romania, the risk of the Vaccine-Associated Paralytic Poliomyelitis cases (VAPP) decreased from less than 2 VAPP cases/year in the 1995-2006 interval to 0 VAPP cases in 2007. The serological study was performed in 2006-2007 only in cases with pair serum samples from 28 acute flaccid paralysis (AFP) cases (age = 3 months - 14 years) and from 45 facial paralysis (FP) cases (age -6 months - 4 years 9 months). A high level of vaccinal coverage was shown for all poliovirus serotypes: >95% in AFP serum samples investigated; and for FP serum samples investigated the levels of antibodies against poliovirus (PV) serotypes were 98% for PV type 1; 87% for PV type 2: and 89% for PV type 3. If the European region is polio free since 2002, the risk of wild PV importation from endemic region remains present. The laboratory capacity for the fast detection and molecular investigations of the emergence of the new epidemic strains and a high level of population immunity must be maintained. A national seroprevalence study concerning all three PV serotypes must be performed.     

No evidence for prolonged excretion of polioviruses in persons with residual paralytic poliomyelitis in Ethiopia, Pakistan and Guatemala.

Persons who have developed acute flaccid paralysis following infection with wild-type polioviruses or vaccine-associated paralytic poliomyelitis usually excrete polioviruses for only a few weeks. However, some patients with paralytic poliomyelitis have had prolonged excretion of polioviruses for periods of up to 10 years after onset of disease. Most prolonged excretors have been identified in industrialized countries. We studied 348 patients 2-28 years old in Ethiopia, Pakistan and Guatemala with residual paralytic poliomyelitis to determine if they had IgA or IgG deficiency or persistent poliomyelitis excretion at least 1 year after onset of disease. None of the 348 affected individuals had IgG deficiency or persistent poliovirus excretion. One child had borderline low serum IgA concentration. Since we did not study children under 2 years of age, persons born with IgG deficiency disorders may have died in developing countries where replacement immunoglobulin therapy is not readily available. Nevertheless, persistent poliovirus excretion among persons 2 years of age and older with residual paralytic poliomyelitis is uncommon in developing countries.     

Viral and host proteins involved in picornavirus life cycle

Picornaviruses cause several diseases, not only in humans but also in various animal hosts. For instance, human enteroviruses can cause hand-foot-and-mouth disease, herpangina, myocarditis, acute flaccid paralysis, acute hemorrhagic conjunctivitis, severe neurological complications, including brainstem encephalitis, meningitis and poliomyelitis, and even death. The interaction between the virus and the host is important for viral replication, virulence and pathogenicity. This article reviews studies of the functions of viral and host factors that are involved in the life cycle of picornavirus. The interactions of viral capsid proteins with host cell receptors is discussed first, and the mechanisms by which the viral and host cell factors are involved in viral replication, viral translation and the switch from translation to RNA replication are then addressed. Understanding how cellular proteins interact with viral RNA or viral proteins, as well as the roles of each in viral infection, will provide insights for the design of novel antiviral agents based on these interactions.     

Environmental surveillance system to track wild poliovirus transmission

Eradication of poliomyelitis from large metropolis cities in India has been difficult due to high population density and the presence of large urban slums. Three paralytic poliomyelitis cases were reported in Mumbai, India, in 1999 and 2000 in spite of high immunization coverage and good-quality supplementary immunization activities. We therefore established a systematic environmental surveillance study by weekly screening of sewage samples from three high-risk slum areas to detect the silent transmission of wild poliovirus. In 2001, from among the 137 sewage samples tested, wild poliovirus type 1 was isolated from 35 and wild poliovirus type 3 was isolated from 1. Acute flaccid paralysis (AFP) surveillance indicated one case of paralytic poliomyelitis from the city. Phylogenetic analysis with complete VP1 sequences revealed that the isolates from environmental samples belonged to four lineages of wild polioviruses recently isolated from poliomyelitis cases in Uttar Pradesh and not to those previously isolated from AFP cases in Mumbai. Wild poliovirus thus introduced caused one case of paralytic poliomyelitis. The virus was detected in environmental samples 3 months before. It was found that wild polioviruses introduced several times during the year circulated in Mumbai for a limited period before being eliminated. Environmental surveillance was found to be sensitive for the detection of wild poliovirus silent transmission. Nucleotide sequence analysis helped identify wild poliovirus reservoir areas.     

Environmental Surveillance System To Track Wild Poliovirus Transmission

Eradication of poliomyelitis from large metropolis cities in India has been difficult due to high population density and the presence of large urban slums. Three paralytic poliomyelitis cases were reported in Mumbai, India, in 1999 and 2000 in spite of high immunization coverage and good-quality supplementary immunization activities. We therefore established a systematic environmental surveillance study by weekly screening of sewage samples from three high-risk slum areas to detect the silent transmission of wild poliovirus. In 2001, from among the 137 sewage samples tested, wild poliovirus type 1 was isolated from 35 and wild poliovirus type 3 was isolated from 1. Acute flaccid paralysis (AFP) surveillance indicated one case of paralytic poliomyelitis from the city. Phylogenetic analysis with complete VP1 sequences revealed that the isolates from environmental samples belonged to four lineages of wild polioviruses recently isolated from poliomyelitis cases in Uttar Pradesh and not to those previously isolated from AFP cases in Mumbai. Wild poliovirus thus introduced caused one case of paralytic poliomyelitis. The virus was detected in environmental samples 3 months before. It was found that wild polioviruses introduced several times during the year circulated in Mumbai for a limited period before being eliminated. Environmental surveillance was found to be sensitive for the detection of wild poliovirus silent transmission. Nucleotide sequence analysis helped identify wild poliovirus reservoir areas.     

Genomic characterization of human and environmental polioviruses isolated in Albania.

Between April and December 1996, a serious outbreak of poliomyelitis occurred in Albania; almost 140 subjects were involved, and the episode presented an unusually high mortality rate (12%). During the outbreak, water samples from the Lana River in Tirana, Albania, and stool samples from two cases of paralytic poliomyelitis were collected and analyzed for the presence of polioviruses. Six polioviruses were isolated from the environmental and human samples, according to standard methods. All the samples were characterized by partial genomic sequencing of 330 bases across the 5' untranslated region (5'-UTR) (nucleotide positions 200 to 530) and of 300 bases across the VP1 region (nucleotide positions 2474 to 2774). Comparison of these sequences with those present in data banks permitted the identification of environmental isolates Lana A and Lana B as, respectively, a Sabin-like type 2 poliovirus and an intertypic recombinant poliovirus (Sabin-like type 2/wild type 1), both bearing a G instead of an A at nucleotide position 481. The two other environmental polioviruses were similar to the isolates from the paralytic cases. They were characterized by a peculiar 5'-UTR and by a VP1 region showing 98% homology with the Albanian epidemic type 1 isolates reported by other authors. This study confirms the environmental circulation in Albania of recombinant poliovirus strains, likely sustained by a massive vaccination effort and by the presence in the environment of a type 1 poliovirus, as isolated from the Lana River in Tirana about 2 months before the first case of symptomatic acute flaccid paralysis was reported in this town.     

Enterovirus 74 Infection in Children

Enterovirus 74 (EV74) is a rarely detected viral infection of children. In 2010, EV74 was identified in New Zealand in a 2 year old child with acute flaccid paralysis (AFP) through routine polio AFP surveillance. A further three cases of EV74 were identified in children within six months. These cases are the first report of EV74 in New Zealand. In this study we describe the near complete genome sequence of four EV74 isolates from New Zealand, which shows only limited sequence identity in the non-structural proteins when compared to the other two known EV74 sequences. As is typical of enteroviruses multiple recombination events were evident, particularly in the P2 region and P3 regions. This is the first complete EV74 genome sequenced from a patient with acute flaccid paralysis.     

Genome-wide sequence analyses of ethnic populations across Russia

The Russian Federation is the largest and one of the most ethnically diverse countries in the world, however no centralized reference database of genetic variation exists to date. Such data are crucial for medical genetics and essential for studying population history. The Genome Russia Project aims at filling this gap by performing whole genome sequencing and analysis of peoples of the Russian Federation.Here we report the characterization of genome-wide variation of 264 healthy adults, including 60 newly sequenced samples. People of Russia carry known and novel genetic variants of adaptive, clinical and functional consequence that in many cases show allele frequency divergence from neighboring populations. Population genetics analyses revealed six phylogeographic partitions among indigenous ethnicities corresponding to their geographic locales. This study presents a characterization of population-specific genomic variation in Russia with results important for medical genetics and for understanding the dynamic population history of the world's largest country.     

Genomic Characterization of Human and Environmental Polioviruses Isolated in Albania

Between April and December 1996, a serious outbreak of poliomyelitis occurred in Albania; almost 140 subjects were involved, and the episode presented an unusually high mortality rate (12%). During the outbreak, water samples from the Lana River in Tirana, Albania, and stool samples from two cases of paralytic poliomyelitis were collected and analyzed for the presence of polioviruses. Six polioviruses were isolated from the environmental and human samples, according to standard methods. All the samples were characterized by partial genomic sequencing of 330 bases across the 5′ untranslated region (5′-UTR) (nucleotide positions 200 to 530) and of 300 bases across the VP1 region (nucleotide positions 2474 to 2774). Comparison of these sequences with those present in data banks permitted the identification of environmental isolates Lana A and Lana B as, respectively, a Sabin-like type 2 poliovirus and an intertypic recombinant poliovirus (Sabin-like type 2/wild type 1), both bearing a G instead of an A at nucleotide position 481. The two other environmental polioviruses were similar to the isolates from the paralytic cases. They were characterized by a peculiar 5′-UTR and by a VP1 region showing 98% homology with the Albanian epidemic type 1 isolates reported by other authors. This study confirms the environmental circulation in Albania of recombinant poliovirus strains, likely sustained by a massive vaccination effort and by the presence in the environment of a type 1 poliovirus, as isolated from the Lana River in Tirana about 2 months before the first case of symptomatic acute flaccid paralysis was reported in this town.     

Acute botulinum-like intoxication by tetanus neurotoxin in mice

Intravenous injection of purified tetanus toxin(1000-0.06 μg) killed mice within minutes(20–450 min), causing flaccid paralysis indistinguishable from that in botulinum intoxication: a linear relation was found between the log of the toxin dose and that of death time(survival time). The dose and route dependences of the manifestations of the spastic paralysis typical of classical tetanus and of the acute botulinum-like flaccid paralysis were studied in relation to the death time. Treatment of the toxin with trypsin or gangliosides did not affect its acute botulinum-like toxicity. Theophylline delayed the time of acute death due to the botulinum-like intoxication in mice caused by tetanus toxin and provided some protection.     

The monkey pathogenicity of the Columbia Sk virus and the mouse-adapted lansing strain of poliomyelitis virus,and the influence of monkey passage on the characteristics of the virus

Summary The intracerebral inoculation of cynomolgus monkeys with Columbia SK virus (mouse brain suspension) produced flaccid paralysis after an incubation period of 3 to 5 days. In the spinal cord leucocytic infiltrations, acute necrosis and neuronophagia of anterior horn cells were found. Similar lesions, but far less extensive were found in the medulla and the brain stem, whereas leucocytic perivascular infiltrations were present in the motor area of the cerebral cortex. Small accumulations of leucocytes were observed in the heart muscle and in the epicardium. The Lansing strain of poliomyelitis virus produced essentially similar lesions, though less extensive, and the incubation period was 14 days. In the heart muscle and the epicardium of a Lansing-infected monkey small mononuclear infiltrations were found. The mouse infectivity titer of the ColSK virus decreased rapidly after monkey passage, and there was a simultaneous decrease of the hemagglutination titer with sheep red cells. No close antigenic relationship between the Y-SK and the ColSK virus was demonstrated by the hemagglutination inhibition reaction with sera from monkeys immunized against Y-SK and ColSK virus. The question is discussed, whether or not the ColSK group of viruses, which should be considered to be of animal origin, has to be classed into the family of poliomyelitis viruses as a fourth immunological type.     

人类肠道病毒B组73、75和97型山东地方株的鉴定及其基因特征分析

本研究对3例急性弛缓性麻痹患者标本的阳性病毒分离物进行了分子生物学定型。按照文献报道的方法,用扩增人类肠道病毒(Human Enterovirus,HEV)VP1完整编码区通用引物008-013、011-012进行逆转录-聚合酶链反应,反应产物纯化后进行序列测定。所得序列通过BLAST程序进行基因定型,显示3株病毒分别为HEV B组中新型病毒HEV73、HEV75和HEV97。将获得的序列与GenBank数据库中已有的各型病毒株VP1基因序列进行同源性分析并构建系统发生树,结果显示与各自的原型株相比有较大的变异,提示本次发现的HEV B组73、75、97型山东地方株与各型原型株相比具有不同的基因特征,这是在国内首次发现HEV97。