Cases Of Paralytic Poliomyelitis Research Articles

Poliomyelitis cases in northern Greece during 1976-1990.

During the period 1976-1990 fourteen cases of paralytic poliomyelitis were recorded in Northern Greece, which has a total population of 2.5 million. Twelve wild strains of poliovirus type-1 were isolated from an equal number of children with paralytic disease from 1976 to 1982. Also, three Sabin-like poliovirus vaccine strains were isolated from two infants with paralytic disease. Since 1985 no paralytic cases have been reported in Northern Greece.

Predictors of Poliomyelitis Case Confirmation at Initial Clinical Evaluation: Implications for Poliomyelitis Eradication in the Americas

In 1985, the Pan American Health Organization adopted the goal of eradication of poliomyelitis from the Americas by 1990. Strategies to accomplish this included high vaccination coverage, aggressive outbreak control, and active surveillance for acute flaccid paralysis (AFP). Although the sensitivity of AFP surveillance for detecting paralytic poliomyelitis cases is high, studies have shown the specificity to be low. In 1990, 2497 notified cases of AFP were investigated in the Americas of which 2146 had stool specimens collected. However, only 18 were confirmed as poliomyelitis by isolation of wild poliovirus from stool specimens, 71 were classified as being compatible with poliomyelitis. Cases of AFP due to causes other than poliomyelitis result in extensive but unnecessary outbreak control measures. To predict, at initial clinical evaluation, the likelihood of future confirmation as a case of poliomyelitis, likelihood ratios (LR) were calculated for different combinations of clinical characteristics of AFP cases (249) from Mexico in 1989 and 1990. The best predictors in a child with AFP were proximal muscle involvement which progressed '4 days together with fever at onset of paralysis, and proximal and unilateral involvement with either fever at onset or paralysis which progressed '4 days. The odds would increase by 12 that the child would eventually be confirmed as poliomyelitis (19), based on a stool culture positive for wild poliovirus (95% confidence interval (CI) 2.6-55.9). A guide for use in the field is proposed whereby local health officials, often with little training in neurological evaluation, can predict at initial clinical examination the likelihood that an AFP case will subsequently be confirmed as poliomyelitis.(ABSTRACT TRUNCATED AT 250 WORDS)

Frequent isolation of intertypic poliovirus recombinants with serotype 2 specificity from vaccine-associated polio cases.

Five representatives from a collection of 21 Sabin type 2-like poliovirus strains isolated from paralytic poliomyelitis cases in two regions of the USSR have been subjected to limited nucleotide sequencing. All proved to be intertypic recombinants having the genes encoding capsid proteins of Sabin 2 origin and a 3'-end portion of the genome derived from either type 1 (3 isolates) or type 3 (2 isolates) Sabin strains. The crossover points in all the 5 genomes have been mapped to different loci of the P3 region. At least 6 additional isolates from the same collection (and 2 isolates from healthy contacts), appeared to have a type 2/type 1 recombinant genome, as judged by oligonucleotide mapping. The biological significance of frequent occurrence of recombinants among field isolates of vaccine-related strains is discussed.

Coupled mutations in the 5'-untranslated region of the Sabin poliovirus strains during in vivo passages: structural and functional implications.

All entero- and rhinovirus RNAs sequenced thus far possess A and U residues at positions corresponding to nucleotides 480 and 525, respectively, of poliovirus type 1. These two nucleotides have been proposed previously to form a base pair. The single exception to this rule appears to be the Sabin type 1 strain, which has a G480. Isolates of the Sabin 1 virus from healthy vaccinees were shown to have either a reversion to A480 or a second-site mutation U525----C, both restoring a potential for efficient base pairing. In vitro translation experiments demonstrated that poliovirus type 1 RNAs with either A480-U525 or G480-C525 are more efficient in promoting translation initiation as compared with the Sabin 1 RNA (G480-U525). The Sabin 2 strain has a U and an A at position 398 and 481, respectively, while its predecessor, strain P712, is shown to have C398 and G481. All the derivatives of the Sabin 2 isolated from vaccine-associated paralytic poliomyelitis cases shown reversion to G481, and most of them reverted also to C398. It is proposed that bases at positions 398 and 481 may be involved in a tertiary interaction. The in vitro template activity of the Sabin type 2 RNA (A481) is significantly lower than that of the isolate RNAs with G481, thus confirming the relation between attenuation and translation efficiency demonstrated previously for the type 1 and type 3 Sabin strains. The C----U change at position 398 exerted only a minor effect on the RNA template activity.

Vaccine-Associated Paralytic Poliomyelitis

We present 10 cases of vaccine-associated paralytic poliomyelitis from Washington State to better acquaint physicians with the signs and symptoms of this condition. Diagnosis may be delayed, and milder cases may be overlooked, owing to the unfamiliarity of physicians with the condition. Based on these 10 cases, a rate of 6.4 cases (recipient plus contact) per million live births is estimated for the period 1966 through 1988 in Washington. This rate is higher than calculated for the nation as a whole. The explantation for this difference is unknown, although several possibilities exist, including case clustering.

Poliomyelitis outbreak in Israel in 1988: a report with two commentaries

An outbreak of 15 cases of paralytic poliomyelitis caused by type 1 poliovirus between July and October, 1988, prompted mass vaccination of the whole Israeli population under the age of 40 years. The focus of the outbreak (12 cases) was the Hadera subdistrict, one of two subdistricts where enhanced inactivated poliovaccine (eIPV) had been the only poliovaccine used for infants since 1982.9 of the 15 victims were 15 years or older, and 9 had previously been immunised with at least three doses of oral poliovaccine (OPV). The authors are divided in their interpretation of the findings. One group considered that the likely causative factors were the greater susceptibility of young adults previously vaccinated with OPV as well as transmission of wild poliovirus to susceptible people by children with low gut immunity against poliovirus after vaccination with eIPV; they concluded that a vaccination programme combining eIPV with OPV is the best option for Israel in future. The other group believed the causative factors were exposure to contaminated sewage or close social contact within the epidemic foci, the presence of an epidemic strain differing from the wild Mahoney and Sabin type 1 vaccine strains, and the lower seropositivity rates and geometric mean titres of neutralising antibodies to the epidemic than to vaccine strains; they believe that eIPV is the means to achieve effective control of poliomyelitis in Israel.

Poliomyelitis Vaccines: Success and Controversy

The conquest of poliomyelitis by killed and live poliomyelitis vaccines is arguably the most successful American public health project. In 1950, 20,000 cases of paralytic poliomyelitis were reported in the United States, whereas in recent years, fewer than 10 cases were reported. These few cases were largely associated with oral vaccine and despite their small number have led to a reconsideration of killed vaccine as a public health measure in the United States.

Observations on the age and spatial distribution of paralytic poliomyelitis in Ibadan, Nigeria

Poliomyelitis (polio) still remains a great public health problem in developing countries. A study of the distribution of 2205 cases of paralytic poliomyelitis seen in Ibadan City, Nigeria over a 15-year period shows that the incidence of polio is much higher in the central core area of the city where sanitary conditions are poor, whereas in the peripheral parts of the city, where environmental sanitation is better, the incidence of polio is lower. A total of 88.4% of the cases originated from the central core area whereas only 11.6% were from the peripheral area. The polio victims from the peripheral area were, however, disproportionately older than the victims from the core area. It is suggested that in the central core area of Ibadan, where children with the highest risk of polio paralysis reside, immunization against polio should be started much earlier, preferably at birth, while children in the peripheral area who may receive their immunization at a later age (6 months and above) will require booster doses at age 15-18 months and at 5 years of age.

Molecular pathogenesis of type 2 poliovirus in mice

Lansing strain of poliovirus type 2 (PV-2) produces a fatal paralytic disease in mice after intracerebral inoculation. To identify virus-containing nerve cells in poliovirus-infected mice, we developed a technique of in situ hybridization for viral RNA with a poliovirus-specific riboprobe. Large numbers of genomes were found in motoneurons and their processes, as well as in ghosts of neurons with or without inflammatory cells. This indicates that the death of motoneurons is due to a direct effect of viral replication. The presence of viral RNA in neuronal processes suggests an axonal dissemination of poliovirus within the central nervous system (CNS). Detection of viral genomes in small cells located in anterior and in posterior horns shows that motoneurons are not the only cells susceptible to poliovirus in the CNS. To see if PV-2/Lansing still exits in nature, PV-2 isolated from the CNS and from the gut of two human cases of paralytic poliomyelitis were characterized by determining epitope maps and phenotypic markers and by sequencing regions of the genome coding for antigenic sites and the 5' non-coding region. Comparison of virus isolated from the intestine and from the CNS of the same subject revealed a high degree of homology, suggesting that virus isolated from the gut is representative of virus in the neuronal lesions. The isolate from a case had more homology to PV-2/Lansing, whereas the other isolate showed more homology to PV-2/Sabin. These results show that, despite intensive vaccination with oral polio vaccine for 25 years, wild PV-2/Lansing-like viruses, pathogenic for mice, still circulate in nature ad induce human paralytic cases.

A new epidemiologic and laboratory classification system for paralytic poliomyelitis cases.

An epidemiologic classification of paralytic poliomyelitis cases (ECPPC) has been in use in the United States since 1976. In 1985, this classification system was reviewed because of recent changes in the epidemiology of paralytic poliomyelitis and improved laboratory capability to definitively characterize poliovirus strains. An alternative classification system was devised, the epidemiologic and laboratory classification of paralytic polio cases (ELCPPC), that incorporated virus isolation and strain characterization with epidemiologic information. Reported paralytic poliomyelitis cases for 1980-86 were classified by both the ECPPC and the ELCPPC classification systems. The new ELCPPC system classified 91 per cent of the reported cases as vaccine-associated, while the ECPPC system classified only 71 per cent of the reported cases as vaccine-associated. The proposed classification system provides more specific and useful information particularly concerning vaccine-associated paralytic poliomyelitis.

Characterisation of two different types of poliovirus isolated from a patient

A clinical case of paralytic poliomyelitis with almost simultaneous isolation of two different types of poliovirus was investigated. A strain of poliovirus type I was isolated from the cerebrospinal fluid and a type 3 strain of poliovirus was isolated from the patient's faeces. Both strains were characterised by two-dimensional oligonucleotide mapping. The type I virus was shown to be of wild type while the type 3 virus was shown to be vaccine-associated.

What Should Polio Immunization Policy Be? Public Health Service Expects Advice Soon

IN A FEW WEEKS, the Public Health Service will receive the advice it sought last year when it commissioned the Institute of Medicine to reevaluate poliomyelitis immunization policy in the United States (<i>JAMA</i>1987;258:2633). The problem centers on the very few cases of paralysis that occur with the use of the live-virus oral vaccine and whether they can be avoided by switching to the inactivated vaccine that carries no such risk. On the average, there are eight cases of paralytic poliomyelitis a year in the United States, directly or indirectly caused by the oral vaccine. So far society has been willing to pay this price to prevent the disease. But changing circumstances are forcing those involved in public health, immunization, and the virology of poliomyelitis to take another look. At a recent two-day meeting, they discussed the issues raised by this situation. In dealing with the problem the essential questions

Vaccination against poliomyelitis: present possibilities and future prospects.

As long as the World Health Organization continues to report that more than 250,000 cases of paralytic poliomyelitis occur annually in developing countries, the United States must be prepared for periodic exposures to wild virus.' Until poliomyelitis is brought under control throughout the world, it behooves us to maintain a high level of vaccine-induced immunity. Hinman and his colleagues from the federal Centers for Disease Control, in the first paper in this series,2 document how well this has been achieved in the nation through the widespread use of OPV. From more than 20,000 cases of paralytic poliomyelitis in 1952, we now have a situation where endogenous wild poliovirus seems to have disappeared from the United States; and when the few imported cases are considered, there is virtually no spread of virus from them. Unfortunately, OPV, like other vaccines, is not perfect, although it is more nearly perfect than most. About five or six vaccine-associated cases now occur per year. Over the past 15 years more cases have occurred in contacts, particularly household contacts, than in the vaccinees. This is not surprising since it was known even before licensing that the virus excreted by vaccinated children was less attenuated than the vaccine itself, having regained some neurovirulence in monkey tests.3 At that time, some recommended that families be vaccinated as units, to avoid exposing susceptibles to mutated virus from the vaccinee. Had that been done, contact cases would have been avoided. The issues raised by the foregoing Hinman/Salk papers2'4 hinge on the possible shift in immunization policy from OPV to IPV. One of the public health axioms on which I was brought up is that if a large-scale program is working wellsuch as reducing the burden of paralytic polio from 20,000 cases per year to less than 10 per year-it should not be tinkered with unless we are certain that the resultant effect will be an improvement. Ifwe had used IPV, it is doubtful that we would have been as successful as the Dutch and the Scandinavians-and even those homogenous populations with their excellent vaccine coverage have had some outbreaks during recent years which, if extrapolated to our large population, would have meant many hundreds of paralytic cases and over a million carriers of wild virus. There is reason to consider a properly timed combination of both IPV and OPV. Such a program would not have any possibility of raising the risk of OPV-associated poliomyelitis and indeed may eliminate cases altogether. Combined IPV/OPV vaccine regimens have proven successful in the tropics where the local population had been subjected to regular and high importation of virus from neighboring countries, resulting in frequent wild virus challenge very early in infancy5'6 In such environments, the killed poliovac-

Live or inactivated poliomyelitis vaccine: an analysis of benefits and risks.

Using decision analysis we evaluated the benefits and risks of continued primary reliance on oral poliomyelitis vaccine (OPV) compared to use of inactivated poliovirus vaccine (IPV). We followed a hypothetical cohort of 3.5 million children from birth to age 30 assuming 95 per cent coverage with 98 per cent effective vaccine. Primary reliance on IPV would result in more cases of paralytic poliomyelitis as well as more susceptibles remaining in the population than would be expected with continuing OPV use (74.1 vs 10.0 cases and 5.9 per cent vs 1.1 per cent susceptibles, respectively). However, with OPV use, most cases of paralysis seen would be associated with the vaccine. Our analysis supports a continuation of current US policy placing primary reliance on OPV but the conclusion is heavily dependent on assumptions of risk of exposure to wild virus in the United States. Major declines in risk of exposure to wild virus could alter the balance significantly.

Experience in Canada with the new revised monkey neurovirulence test for oral poliovirus vaccine

Nine years of experience in our laboratory, using more than 1500 cynomolgus monkeys in 138 tests, has shown that the new neurovirulence test (NVT) adopted by the World Health Organization (WHO) for live, oral monovalent vaccine of each poliovirus type, was a reproducible and sensitive assay likely to ensure the safety of this vaccine in humans. Our findings were the following: (1) when the test vaccine and the appropriate homotypic reference vaccine were tested in a single group of monkeys, the concurrent use of the reference vaccine considerably increased the reproducibility of the NVT; (2) in the assessment of the degree of attenuation of each lot of vaccine, the use of 12 monkeys for types 1 and 2 vaccines and 20 monkeys for type 3 vaccine (inoculated intraspinally each for reference and test vaccine) was satisfactory; (3) the virus dose used per monkey (10 5.6 to 10 6.6 pfu per monkey) was found not to be critical, i.e. the lower virus dose yielded mean lesion scores in the central nervous system of monkeys at least as high or higher than the tenfold higher virus dose; (4) the statistical analysis of our data showed that the old intrathalamic (IT) assay was considerably less sensitive than the new intraspinal (IS) assay, i.e., a test vaccine with a twofold increase in monkey neurovirulence would have a 41% chance of failing in the IT test (using 30 monkeys per vaccine), while this chance increased to 99% in the WHO IS assay (using 12 or 20 monkeys per vaccine). Since the introduction of the WHO NVT in Canada, the laboratory findings in monkeys were confirmed by vaccine experience in humans; the number of vaccine-associated paralytic poliomyelitis cases in the population showed a further decline.

Rationale for the sequential use of inactivated poliovirus vaccine and live attenuated poliovirus vaccine for routine poliomyelitis immunization in the United States.

Despite the concerns mentioned in the last section, there are many reasons to believe that a polio immunization schedule that incorporates sequential doses of inactivated poliovirus vaccine and live attenuated poliovirus vaccine would provide both humoral and intestinal immunity to the fully immunized person that is at least as good, if not better, than the immunity achieved by the use of IPV or OPV alone. A substantial degree of protection should also extend to partially immunized and unimmunized preschool aged children in the community. Furthermore most of the cases of OPV-associated paralytic poliomyelitis could be prevented. Because the reasons for these beliefs are based on data from small studies and on inferences from related research, specific recommendations for a change from current polio immunization policy must depend on additional clinical research. Well-designed trials comparing several different options for sequencing both inactivated and live vaccines are needed, and these studies should focus carefully on both humoral and intestinal immunity conferred by the various vaccine schedules.

Importation of poliomyelitis to industrialised nations between 1975 and 1984: evaluation and conclusions for vaccination recommendations.

World Health Organisation and public health authority records show that 175 cases of paralytic poliomyelitis were imported to industrialised countries between 1975 and 1984. Detailed case reports were therefore analysed to identify characteristic features associated with acquisition of the infection. Of the 175 cases, 96 (55%) were diagnosed in foreign workers or their families, 47 (27%) in nationals travelling on holiday or business, 11 (6%) in immigrants, and 21 (12%) either in contacts who had not travelled or in unclassified groups. Poliomyelitis principally affected children under 5, but travellers aged 41-65 had the highest case fatality rate. The main serotype isolated was poliovirus type 1. The findings suggest that though fewer than one in every 100,000 travellers may be infected by poliomyelitis, all travellers and all immigrants, refugees, and foreign workers should be given full protection against all three polioviruses by routine vaccination.

Poliomyelitis in Spain, 1982-1984: virologic and epidemiologic studies.

The authors present a detailed study of poliomyelitis in Spain for the years 1982, 1983, and 1984. The 50 cases reported have been epidemiologically classified following World Health Organization guidelines. Virus was isolated from 43 of these cases. Intratypic characterization was done using specifically absorbed antisera classifying the strains as non-Sabin-like and Sabin-like. The neutralizing antibodies in whole and fractionated sera were also determined. The largest number of paralytic poliomyelitis cases, 28, was found in children in the first year of life. Thirty of the cases were unvaccinated children. Poliomyelitis was not detected in adults during the period described. Wild strains isolated were type I and III, primarily from Gypsies. There was a significant incidence of vaccine-associated cases in recipients, as well as in contacts during 1982 and 1983. The cases were located in the Mediterranean and Southern zone. In 1984, total and vaccine-associated cases dropped dramatically.

Immunizations, Immunoprophylaxis, and Chemoprophylaxis to Prevent Selected Infections

VACCINES have played a vital role in improving health care in the United States. One need only remember that from 1951 to 1955 the United States averaged more than 35 000 cases of paralytic poliomyelitis annually, whereas in 1984 there were only eight reported cases. Nonetheless, there continue to be difficulties with immunization programs. Complacency is a major one; there are times when the glamour of modern curative medicine has overshadowed the steady, undramatic activities involved in immunization programs. This is particularly true when adult immunizations are considered. The emphasis on disease prevention, so dominant in the training of pediatricians, has not been as strong in the training received by US internists or general practitioners. The low 20% figure of yearly influenza immunizations given to high-risk patients is eloquent but sad testimony to this problem. Table 1 summarizes commonly used vaccines and immunoprophylactic agents. This review briefly describes the efficacy

Vaccine-Associated Paralytic Poliomyelitis

From 1973 through 1984, there were 138 cases of paralytic poliomyelitis reported in the United States; 105 (76%) were vaccine associated. Of the 105 vaccine-associated cases, 35 occurred in recipients of oral polio vaccine (OPV), 50 in contacts to OPV recipients, 14 in immune deficient individuals, and six in individuals who had no history of receiving OPV or contact with recent OPV recipients. Thirty-three (94%) of the recipient cases, 41 (82%) of the contact cases, and five (36%) of the immune deficient cases were associated with the first dose of OPV. The overall frequency of vaccine-associated poliomyelitis was one case per 2.6 million doses distributed. However, the relative frequency of paralysis associated with the first dose in the OPV series was one case per 520,000 doses vs one case per 12.3 million subsequent doses. Vaccine-associated paralytic poliomyelitis is rare and the risks of OPV are small. The greatest likelihood of paralysis occurs in association with the first dose of OPV and that likelihood is reduced in subsequent doses more for recipients than for their contacts.