We describe a case of abortive poliomyelitis due to poliovirus type 3 (PV3) in an unvaccinated woman and a subclinical poliovirus infection in her family during an epidemic in the Netherlands. The woman excreted the epidemic strain (PV3) for 7 weeks. Her two children received oral attenuated poliovirus vaccine and were subsequently found to excrete PV1 and PV2 vaccine strains in addition to the epidemic PV3 strain. Her husband, who had neutralizing antibodies to all three poliovirus types because of previous vaccination, initially excreted no virus; subsequently, however, the vaccine strain PV1 and the epidemic strain PV3 could be cultured from his feces. These observations demonstrate the ease with which poliovirus circulates among family members, including those with neutralizing antibodies.

We report an infant case of acute fulminant myocarditis which occurred after administration of a diphtheria, polio, and tetanus vaccination. Fever and dyspnea developed after the vaccination. Extracorporeal membrane oxygenation was used for intractable cardiogenic shock. The patient survived the extracorporeal support, but poor ventricular contractility recurred 2 months later and she died while waiting for heart transplantation.

The authors report the case of a 26 year old woman with acute anterior poliomyelitis contracted during the vaccination of her baby. Despite having been herself vaccinated in infancy she was not protected against the poliovirus. The clinical interest of this uncommon case is a severe paralytic state with definitive paraplegia. The authors suggest serologic testing of patients born before 1967 especially if they are at risk of encountering the virus.

Autism is a highly heritable behavioral disorder. Yet, two decades of genetic investigation have unveiled extremely few cases that can be solely explained on the basis of de novo mutations or cytogenetic abnormalities. Vertical viral transmission represents a nongenetic mechanism of disease compatible with high parent-to-offspring transmission and with low rates of disease-specific genetic abnormalities. Vertically transmitted viruses should be found more frequently in the affected tissues of autistic individuals compared to controls. Our initial step was thus to assess by nested polymerase chain reaction (PCR) and DNA sequence analysis the presence of cytomegalovirus (CMV), Epstein-Barr virus (EBV), herpes simplex virus type 1 (HSV1), herpes simplex virus type 2 (HSV2), human herpes virus 6 (HHV6), BK virus (BKV), JC virus (JCV), and simian virus 40 (SV40) in genomic DNA extracted from postmortem temporocortical tissue (Brodmann areas 41/42) belonging to 15 autistic patients and 13 controls. BKV, JCV, and SV40 combined are significantly more frequent among autistic patients compared to controls (67% versus 23%, respectively; P<.05). The majority of positives yielded archetypal sequences, whereas six patients and two controls unveiled single-base pair changes in two or more sequenced clones. No association is present with the remaining viruses, which are found in relatively few individuals (N

Revaxis(®) is a vaccine against diphtheria, tetanus and poliomyelitis (dT-IPV). This vaccine should not be administered by the intradermal or intravenous route. Poor injection techniques and related consequences are rare. We report a case of bursitis associated with reactive glenohumeral effusion complicated by bone erosion occurring after injection of the dT-IPV vaccine. A 26 year old patient was admitted for painful left shoulder causing functional impairment. Control magnetic resonance imaging showed bone oedema on the upper outer part of the humeral head, with a slight cortical irregularity, indicating that the vaccine was injected in contact with the bone at this location, causing erosion. Outcome was favourable after intra-articular corticosteroids. Reports of articular or periarticular injury after vaccination are extremely rare, in view of the substantial number of vaccines administeredevery year. The potential complications of vaccination are well known to general practitioners but under-reported in the literature.

Poliomyelitis caused by wild poliovirus has been virtually nonexistent in the United States since 1980, and vaccine-associated paralytic poliomyelitis (VAPP) has emerged as the predominant form of the disease. We reviewed national surveillance data on poliomyelitis for 1960-1989 to assess the changing risks of wild-virus, vaccine-associated, and imported paralytic disease; we also sought to characterize the epidemiology of poliomyelitis for the period 1980-1989. The risk of VAPP has remained exceedingly low but stable since the mid-1960s, with approximately 1 case occurring per 2.5 million doses of oral poliovirus vaccine (OPV) distributed during 1980-1989. Since 1980 no indigenous cases of wild-virus disease, 80 cases of VAPP, and five cases of imported disease have been reported in the United States. Three distinct groups are at risk of vaccine-associated disease: recipients of OPV (usually infants receiving their first dose), persons in contact with OPV recipients (mostly unvaccinated or inadequately vaccinated adults), and immunologically abnormal individuals. Overall, 93% of cases in OPV recipients and 76% of vaccine-associated cases have been related to administration of the first or second dose of OPV. Our findings suggest that adoption of a sequential vaccination schedule (inactivated poliovirus vaccine followed by OPV) would be effective in decreasing the risk of VAPP while retaining the proven public health benefits of OPV.

BACKGROUND:Individuals who chronically excrete neurovirulent poliovirus of vaccine-origin are of considerable concern to the Global Polio Eradication programme. Chronic infection with such polioviruses is a recognised complication of hypogammaglobulinaemia.

METHODS:We did a series of in-vitro and in-vivo therapeutic studies, with a view to clearing persistent neurovirulent poliovirus infection in an individual with common variable immunodeficiency, using oral immunoglobulin, breast milk (as a source of secretory IgA), ribavirin, and the anti-picornaviral agent pleconaril. We undertook viral quantitation, antibody neutralisation and drug susceptibility assays, and viral gene sequencing.

FINDINGS:Long-term asymptomatic excretion of vaccine-derived neurovirulent poliovirus 2 was identified in this hypogammaglobulinaemic man, and was estimated to have persisted for up to 22 years. Despite demonstrable in-vitro neutralising activity of immunoglobulin and breast milk, and in-vitro antiviral activity of ribavirin, no treatment was successful at clearing the virus, although in one trial breast milk significantly reduced excretion levels temporarily. During the course of study, the virus developed reduced susceptibility to pleconaril, precluding the in-vivo use of this drug. Sequence analysis revealed the emergence of a methionine to leucine mutation adjacent to the likely binding site of pleconaril in these isolates.

INTERPRETATION:Chronic vaccine-associated poliovirus infection in hypogammaglobulinaemia is a difficult condition to treat. It represents a risk to the strategy to discontinue polio vaccination once global eradication has been achieved.

Irreparable damage to the anterior horn cells of the cervical and thoracic cord was found in a 20-week-old fetus whose mother was immune to poliomyelitis before conceiving but who was inadvertently given oral polio vaccine at 18 weeks gestation. Polio neutralizing antibody titres in sera, taken before and after pregnancy, were identical and were at levels normally regarded as providing protection. Unsuccessful attempts were made to isolate poliovirus from extracts of fetal brain, lung, liver and placenta. Fluorescent antibody tests were performed on various levels of the central nervous system and on the left and right extensor forearm muscles. Specific positive fluorescence to poliovirus 2 and 3 antigens was detected at dorsal spinal cord level only. One positive result was seen with Coxsackie A9 antiserum and fresh guinea-pig complement in the inflammatory cells in the right extensor forearm muscles.This experience, as yet unexplained, underlines the importance of ensuring that women are not pregnant prior to oral polio vaccination.

Paralytic poliomyelitis is rare in the United States because of the success of universal childhood immunization and the Global Polio Eradication Initiative. Poliovirus vaccine was introduced in the 1950s. Since then, the United States has eliminated indigenous wild poliovirus transmission, controlled imported wild poliovirus cases, and, through a vaccine policy change (i.e., from live, attenuated oral polio vaccine [OPV] to inactivated polio vaccine [IPV]), eliminated vaccine-associated paralytic polio (VAPP) cases. The most recent VAPP case occurred in 1999. The primary risk for paralytic polio for U.S. residents is through travel to countries where polio remains endemic or where polio outbreaks are occurring. This report describes the first known occurrence of imported VAPP in an unvaccinated U.S. adult who traveled abroad, where she likely was exposed through contact with an infant recently vaccinated with OPV. This case highlights the previously unrecognized risk for paralytic polio among unvaccinated persons exposed to OPV during travel abroad.

BACKGROUND: The 2-fold increase in female mortality after high-titer measles vaccine may have occurred because many children received diphtheria-tetanus-pertussis (DTP) vaccine or inactivated polio vaccine (IPV) after high-titer measles vaccine.

OBJECTIVE: We examined whether DTP vaccine and IPV were associated with increased female mortality when they were the most recent vaccine administered to children who had not received measles vaccine. Setting and Design: IPV was used as a control vaccine in 4 randomized trials of early measles vaccination (MV) with enrollment at 4-6 months of age conducted in Guinea-Bissau. Many children had not received all 3 DTP vaccinations before enrollment, and therefore received DTP after IPV or MV. We examined whether DTP vaccination status at enrollment affected the female-male mortality ratio. Population: 9544 children enrolled in 4 trials. Main outcome measure: The female-male mortality ratio in different vaccine groups.

RESULTS: Females had a higher mortality rate than males among children randomized to receive IPV (mortality rate ratio [MR] 1.52, 95% CI 1.02-2.28), but females had a similar mortality rate to males among children randomized to receive MV (MR 1.01, 0.69-1.46) and among children in the IPV group after they had received MV at 9 months of age or later (MR 0.88, 0.68-1.14). Children who had not received a third dose of DTP before enrollment (and were likely to receive DTP after MV or IPV) tended to have a higher mortality than children who had received all 3 doses of DTP (MR 1.30, 0.97-1.73). This effect was seen only among girls (MR 1.61, 1.08-2.40) and not among boys (MR 1.02, 0.67-1.54). Girls had a lower mortality when MV was the most recent vaccine received rather than DTP or IPV (MR 0.49, 0.28-0.87).

CONCLUSIONS: Randomization to IPV was associated with higher female than male mortality. However, the increased female mortality might result from additional doses of DTP received after enrollment and before measles vaccination.

A type 2 vaccine-derived poliovirus (VDPV), differing from Sabin 2 at 2.5% (22/903) of VP1 nucleotide (nt) positions, was isolated from an incompletely immunized 21-month-old Nigerian child who developed acute flaccid paralysis in 2002. Sequences upstream of nt position 620 (within the 5'-untranslated region [5'-UTR]) and downstream of nt position 5840 (in the 3C(pro) region) were derived from species C enteroviruses unrelated to the oral poliovirus vaccine (OPV) strains. The two substitutions associated with the attenuated phenotype had either recombined out (A(481)-->G in the 5'-UTR) or reverted (Ile(143)-->Thr in VP1). The VDPV isolate had lost the temperature sensitive phenotype of Sabin 2 and it was antigenically distinct from the parental OPV strain, having amino acid substitutions in or near neutralizing antigenic sites 1 and 3. The date of the initiating OPV dose, calculated from the number of synonymous substitutions in the capsid region, was estimated to be approximately 16 to 18 months before onset of paralysis, a finding inconsistent with the most recent mass OPV campaign (conducted 12 days before onset of paralysis) as being the source of infection. Although no related type 2 VDPVs were detected in Nigeria or elsewhere, the VDPV was found in an area where conditions favor VDPV emergence and spread.

Although acute flaccid paralysis is a manifestation observed in several neurologic and muscular disorders, vaccine-associated paralytic poliomyelitis (VAPP) is an exceedingly rare etiology. In the clinical setting of acute flaccid paralysis, MRI is useful in differentiating between VAPP and other conditions. Additionally, MRI can assess the extent of lesions. However, reports on MRI findings in VAPP are scarce in the pediatric radiology literature. We report a Brazilian infant who developed VAPP 40 days after receiving the first dose of oral polio vaccine (OPV). MR images of the cervical and thoracic spinal cord showed lesions involving the anterior horn cell, with increased signal intensity on T2-weighted sequences. We would like to emphasize the importance of considering VAPP as a differential diagnosis in patients with acute flaccid paralysis and an MRI showing involvement of medulla oblongata or spinal cord, particularly in countries where OPV is extensively administered.

Neonatal poliomyelitis, which was rare even when poliomyelitis was widespread, has not been reported in the United States since use of live oral poliovirus vaccine (Sabin's vaccine) became widespread. We report a child who became symptomatic with apnea at 18 days of age and who subsequently developed a permanent monoparesis. Serologic and cultural evidence indicated the virus as poliovirus vaccine type. Another infant who received live oral poliovirus vaccine was probably the source of the infecting virus. Recognition that poliovirus infection can still occur in the United States and an understanding of the serologic, cultural, and typing tests required to substantiate this diagnosis are needed so that such patients will be accurately diagnosed.

Between April 1982 and June 1983 four children 3 to 24 months of age were referred for evaluation of neurologic abnormalities found to be compatible with vaccine-related poliovirus infection, which had not been suspected by referring physicians. Patients were epidemiologically unrelated residents of Indiana, and none had prior symptoms suggestive of immunodeficiency. All had received poliovirus vaccine orally (first dose in three, fourth dose in one) and a diphtheria-tetanus-pertussis injection in the left anterior thigh within 30 days of symptoms. A vaccine-like strain of poliovirus was isolated from each patient, and each had symptoms (left leg paralysis in three; developmental regression, spasticity, and progressive fatal cerebral atrophy in one) persisting for at least 6 months. Immune function was normal in two with poliovirus type 3 infection, and abnormal (hypogammaglobulinemia, combined immunodeficiency) in two with type 1 and type 2 infection, respectively. The incidence of observed vaccine-related poliovirus infection in Indiana recipients of orally administered poliovirus vaccine was 0.058 per 100,000 per year, significantly greater (P less than 0.001) than predicted.

We report a case of vaccine-associated paralytic poliomyelitis (VAPP) in Bahrain. The case occurred in an 8-week-old infant who had received a dose of oral polio vaccine (OPV) 7 days after birth. She was in contact with two vaccinees who had received OPV during the national immunisation campaign conducted 10 days before her birth. Specimens from the infant were sent to the WHO Collaborating Centre for Virus Reference and Research Laboratory for serological testing and virus detection, including genomic sequencing. Clinical and virological features are presented of a case of VAPP caused by the Sabin 3 strain of poliovirus that had reverted towards neurovirulence. The case represents one in 51,879 first doses of OPV distributed between 1995 and 1998. In order to reduce further the risk of VAPP, the dose of OPV at birth has been discontinued and a sequential schedule of inactivated polio vaccine (IPV) followed by OPV will be recommended.

A cytopathic 'stealth' virus was cultured from the cerebrospinal fluid of a patient with a bipolar psychotic disorder who developed a severe encephalopathy leading to a vegetative state. DNA sequencing of a polymerase chain reaction-amplified product from infected cultures has identified the virus as an African green monkey simian cytomegalovirus (SCMV)-related stealth virus. The virus is similar to the SCMV-related stealth virus isolated from a patient with chronic fatigue syndrome. The findings support the concepts that stealth viruses can account for a spectrum of dysfunctional brain diseases and that some of these viruses may have arisen from live polio viral vaccines.

The simultaneous sudden deaths of twins rarely occur and therefore it has received limited attention in the medical literature. When the deaths of the twins meet the defined criteria for sudden infant death syndrome (SIDS) independently and take place within the same 24 h range it can be called as simultaneous SIDS (SSIDS). The case(s): Twin girls (3.5-month-old) were found dead by their mother in their crib, both in supine position. The infants were identical twins and delivered at a hospital by cesarean section. Both infants were healthy and did not have any serious medical history. Two days prior to the incident, the twins had received the second dose of oral polio, DPT and the first dose of hepatitis B vaccines and they had fever on the first day of the vaccination and been given teaspoonful of acetaminophen. Death scene investigation, judicial investigation, parental assessment, macroscopic and microscopic autopsy findings and the toxicological analysis did not yield any specific cause of death. The case(s) were referred to a supreme board composed of multidisciplinary medical professionals at the Institute of Forensic Medicine, Ministry of Justice, in Istanbul. The Board decided that the available data was consistent with SIDS. These SIDS case(s) are presented because twin SIDS are rare and this is the first time that a simultaneous twin SIDS have been reported in Turkey. Simultaneous SIDS cases have many implications regarding definition, diagnosis and medico-legal approach.

Some polio vaccines prepared from 1954 to 1961 were contaminated with infectious SV40. It has been assumed that all polio vaccines were SV40 free in the United States after 1961 and in other countries after 1962. Following a WHO requirement that was prompted by the detection of SV40 in some human tumors, we conducted a multilaboratory study to test for SV40 polio vaccines prepared after 1961. Vaccine samples from 13 countries and the WHO seed were initially tested by PCR. The possible presence of intact and/or infectious SV40 DNA in PCR-positive samples was tested by transfection and infection of permissive CV-1 cells. All results were verified by immunohistochemistry, cloning, and sequencing. All the vaccines were SV40 free, except for vaccines from a major eastern European manufacturer that contained infectious SV40. We determined that the procedure used by this manufacturer to inactivate SV40 in oral poliovirus vaccine seed stocks based on heat inactivation in the presence of MgCl2 did not completely inactivate SV40. These SV40-contaminated vaccines were produced from early 1960s to about 1978 and were used throughout the world. Our findings underscore the potential risks of using primary monkey cells for preparing poliovirus vaccines, because of the possible contamination with SV40 or other monkey viruses, and emphasize the importance of using well-characterized cell substrates that are free from adventitious agents. Moreover, our results indicate possible geographic differences in SV40 exposure and offer a possible explanation for the different percentage of SV40-positive tumors detected in some laboratories.

A pediatric patient, who was given live-attenuated oral polio vaccine twice without distinct gait disturbance during infancy, begun to present limp at 3 years. His gait disturbance became remarkable with aging. At 7 years, he was unable to dorsiflex the left ankle, and presented flaccid monoplegia of the left lower extremity, and the left Achilles tendon reflex was diminished. Magnetic resonance imaging revealed multiple crack-lines in the left anterior tibial muscle, but was unable to detect any distinct lesion at responsible level of L4, L5 and S1 anterior horn cells' degeneration. Electromyography showed continuous fibrillation potentials, but muscle biopsy presented nearly normal in this muscle. The serum levels of polio antibody type 1 and type 2 titers were elevated 64× respectively, while the type 3 antibody titer was not elevated 4×. This patient was diagnosed as live attenuated oral polio vaccine-related flaccid monoplegia, with mild clinical course.

Oral poliovirus vaccine (OPV) can cause, in extremely rare cases vaccine-associated paralytic poliomyelitis in recipients, or contacts of vaccinees. Three cases of vaccine-associated paralytic poliomyelitis (two contacts and one recipient) occurred in the Bourgas region of Bulgaria in the spring of 2006. The first two cases, notified as acute flaccid paralysis, were 55 days old unvaccinated twin brothers, having been in contact with vaccinees. The third case concerned a 4-month-old infant who had received the first OPV dose 37 days prior to the onset of illness. Complete clinical, epidemiological, virological, serological and molecular investigations of the children with paralysis and their contacts were undertaken. In all the three cases type 3 polioviruses were isolated from fecal samples and characterized as Sabin-like poliovirus strains. Type 3 polioviruses isolated from the twin brothers demonstrated by sequence analysis U-to-C back mutation at nt 472 of the 5' UTR, known to correlate with neurovirulence, and mutation in the VP1 region. Type 3 poliovirus isolated from the third child demonstrated in the 3D sequenced region a recombination with Sabin type 1 poliovirus. In the latter region, three silent mutations and one, resulting in amino acid substitution, were also observed. The clinical, epidemiological and virological data and the neurological sequelae observed 60 days following the onset of paralysis, confirmed the diagnosis of vaccine-associated paralytic poliomyelitis in all the three patients.