Poliovirus surveillance: isolation of polioviruses in Japan, 1980-1991. A report of the National Epidemiological Surveillance of Infectious Agents in Japan.

This report presents an overall distribution of poliovirus isolations in Japan, where poliomyelitis has been under control over two decades as a result of legal administration of two doses of the trivalent live oral poliovirus vaccine of the Sabin strains (OPV) to children under 48 months of age. During the past 12 years from 1980 through 1991, a total of 1,126 poliovirus isolations from humans and 268 isolations from sewage/river water were reported by respectively 49 and nine of the participating laboratories. Type 2 was most frequently isolated from children after administration of one dose of OPV, followed by type 1 and type 3. On the contrary, after the second dose of OPV, the rate of isolation of type 3 exceeded those of type 2 and type 1. Seasonal and age distribution of poliovirus isolations from both humans and sewage/river water paralleled the OPV vaccination schedule in Japan. One percent of the isolations were, however, from infants younger than the vaccination-scheduled ages and 5% were from children older than those ages, including one each from 15 and 16 years olds. The data indicate that the poliovirus has silently been disseminated from vaccinated children to others and the community, thus suggesting repeated transmission of the viruses. The fact that some elder children had poliovirus colonization in their alimentary tracts indicates a potential risk of infection of such a population when exposed to a wild virus and of becoming a source of transmission to others.     

Circulation of endemic type 2 vaccine-derived poliovirus in Egypt from 1983 to 1993

From 1988 to 1993, 30 cases of poliomyelitis associated with poliovirus type 2 were found in seven governorates of Egypt. Because many of the cases were geographically and temporally clustered and because the case isolates differed antigenically from the vaccine strain, it was initially assumed that the cases signaled the continued circulation of wild type 2 poliovirus. However, comparison of sequences encoding the major capsid protein, VP1 (903 nucleotides), revealed that the isolates were related (93 to 97% nucleotide sequence identity) to the Sabin type 2 oral poliovirus vaccine (OPV) strain and unrelated (<82% nucleotide sequence identity) to the wild type 2 polioviruses previously indigenous to Egypt (last known isolate: 1979) or to any contemporary wild type 2 polioviruses found elsewhere. The rate and pattern of VP1 divergence among the circulating vaccine-derived poliovirus (cVDPV) isolates suggested that all lineages were derived from a single OPV infection that occurred around 1983 and that progeny from the initiating infection circulated for approximately a decade within Egypt along several independent chains of transmission. Complete genomic sequences of an early (1988) and a late (1993) cVDPV isolate revealed that their 5' untranslated region (5' UTR) and noncapsid- 3' UTR sequences were derived from other species C enteroviruses. Circulation of type 2 cVDPVs occurred at a time of low OPV coverage in the affected communities and ceased when OPV coverage rates increased. The potential for cVDPVs to circulate in populations with low immunity to poliovirus has important implications for current and future strategies to eradicate polio worldwide.     

Intratypic recombination among lineages of type 1 vaccine-derived poliovirus emerging during chronic infection of an immunodeficient patient

We determined the complete genomic sequences of nine type 1 immunodeficient vaccine-derived poliovirus (iVDPV) isolates obtained over a 337-day period from a poliomyelitis patient from Taiwan with common variable immunodeficiency. The iVDPV isolates differed from the Sabin type 1 oral poliovirus vaccine (OPV) strain at 1.84% to 3.15% of total open reading frame positions and had diverged into at least five distinct lineages. Phylogenetic analysis suggested that the chronic infection was initiated by the fifth and last OPV dose, given 567 days before onset of paralysis, and that divergence of major lineages began very early in the chronic infection. Key determinants of attenuation in Sabin 1 had reverted in the iVDPV isolates, and representative isolates of each lineage showed increased neurovirulence for PVR-Tg21 transgenic mice. None of the isolates had retained the temperature-sensitive phenotype of Sabin 1. All isolates were antigenic variants of Sabin 1, having multiple amino acid substitutions within or near neutralizing antigenic sites 1, 2, and 3a. Antigenic divergence of the iVDPV variants from Sabin 1 followed two major independent evolutionary pathways. The emergence of distinct coreplicating lineages suggests that iVDPVs can replicate for many months at separate sites in the gastrointestinal tract. Some isolates had mosaic genome structures indicative of recombination across and within lineages. iVDPV excretion apparently ceased after 30 to 35 months of chronic infection. The appearance of a chronic VDPV excretor in a tropical, developing country has important implications for the strategy to stop OPV immunization after eradication of wild polioviruses.     

Multiscale model for forecasting Sabin 2 vaccine virus household and community transmission

Since the global withdrawal of Sabin 2 oral poliovirus vaccine (OPV) from routine immunization, the Global Polio Eradication Initiative (GPEI) has reported multiple circulating vaccine-derived poliovirus type 2 (cVDPV2) outbreaks. Here, we generated an agent-based, mechanistic model designed to assess OPV-related vaccine virus transmission risk in populations with heterogeneous immunity, demography, and social mixing patterns. To showcase the utility of our model, we present a simulation of mOPV2-related Sabin 2 transmission in rural Matlab, Bangladesh based on stool samples collected from infants and their household contacts during an mOPV2 clinical trial. Sabin 2 transmission following the mOPV2 clinical trial was replicated by specifying multiple, heterogeneous contact rates based on household and community membership. Once calibrated, the model generated Matlab-specific insights regarding poliovirus transmission following an accidental point importation or mass vaccination event. We also show that assuming homogeneous contact rates (mass action), as is common of poliovirus forecast models, does not accurately represent the clinical trial and risks overestimating forecasted poliovirus outbreak probability. Our study identifies household and community structure as an important source of transmission heterogeneity when assessing OPV-related transmission risk and provides a calibratable framework for expanding these analyses to other populations.Trial Registration: ClinicalTrials.gov This trial is registered with clinicaltrials.gov, {"type":"clinical-trial","attrs":{"text":"NCT02477046","term_id":"NCT02477046"}}NCT02477046.     

Circulation of type 1 vaccine-derived poliovirus in the Philippines in 2001

In 2001, highly evolved type 1 circulating vaccine-derived poliovirus (cVDPV) was isolated from three acute flaccid paralysis patients and one contact from three separate communities in the Philippines. Complete genomic sequencing of these four cVDPV isolates revealed that the capsid region was derived from the Sabin 1 vaccine strain but most of the noncapsid region was derived from an unidentified enterovirus unrelated to the oral poliovirus vaccine (OPV) strains. The sequences of the cVDPV isolates were closely related to each other, and the isolates had a common recombination site. Most of the genetic and biological properties of the cVDPV isolates were indistinguishable from those of wild polioviruses. However, the most recently identified cVDPV isolate from a healthy contact retained the temperature sensitivity and partial attenuation phenotypes. The sequence relationships among the isolates and Sabin 1 suggested that cVDPV originated from an OPV dose given in 1998 to 1999 and that cVDPV circulated along a narrow chain of transmission. Type 1 cVDPV was last detected in the Philippines in September 2001, and population immunity to polio was raised by extensive OPV campaigns in late 2001 and early 2002.     

Vaccine-derived polioviruses.

The Sabin oral poliovaccine (OPV) is extremely efficacious and safe, despite its inherent genetic instability. While reversion to nearly wild-type phenotype regularly occurs soon after the onset of OPV reproduction in the gastro-intestinal tract of vaccine recipients or their contacts, this is usually not a big problem, provided the vaccine is used either for mass vaccination or in populations with a relatively high level of anti-polio immunity. However, if these conditions are not met, the vaccine viruses are likely to be converted into highly transmissible agents with a nearly wild-type level of neurovirulence. Moreover, OPV viruses may persist and evolve even in adequately immunized populations. The current strategy for the "endgame" of poliovirus eradication envisions cessation of OPV usage shortly after the last isolation of a wild poliovirus. If implemented, this strategy would result in rapid growth of non-immune human populations at the time when OPV derivatives would very likely be persisting. Therefore, the planned cessation of OPV vaccination is associated with a very high, and in the author's opinion, unacceptable risk of polio outbreaks caused by OPV derivatives. The only currently available tool to curb such outbreaks is OPV, which should have been used at a global scale. Safe discontinuation of OPV vaccination will be possible only after an efficient new vaccine or an anti-poliovirus drug is available. To achieve this goal, stimulation of poliovirus research and elimination of organizational and financial obstacles preventing it are needed.     

Cold chain and virus‐free chloroplast‐made booster vaccine to confer immunity against different poliovirus serotypes

The WHO recommends complete withdrawal of oral polio vaccine (OPV) type 2 by April 2016 globally and replacing with at least one dose of inactivated poliovirus vaccine (IPV). However, high‐cost, limited supply of IPV, persistent circulating vaccine‐derived polioviruses transmission and need for subsequent boosters remain unresolved. To meet this critical need, a novel strategy of a low‐cost cold chain‐free plant‐made viral protein 1 (VP1) subunit oral booster vaccine after single IPV dose is reported. Codon optimization of the VP1 gene enhanced expression by 50‐fold in chloroplasts. Oral boosting of VP1 expressed in plant cells with plant‐derived adjuvants after single priming with IPV significantly increased VP1‐IgG1 and VP1‐IgA titres when compared to lower IgG1 or negligible IgA titres with IPV injections. IgA plays a pivotal role in polio eradication because of its transmission through contaminated water or sewer systems. Neutralizing antibody titres (~3.17–10.17 log₂ titre) and seropositivity (70–90%) against all three poliovirus Sabin serotypes were observed with two doses of IPV and plant‐cell oral boosters but single dose of IPV resulted in poor neutralization. Lyophilized plant cells expressing VP1 stored at ambient temperature maintained efficacy and preserved antigen folding/assembly indefinitely, thereby eliminating cold chain currently required for all vaccines. Replacement of OPV with this booster vaccine and the next steps in clinical translation of FDA‐approved antigens and adjuvants are discussed.     

A vision of a world without polio: the OPV cessation strategy.

Once the eradication of wild poliovirus has been confirmed, the public health benefits of routine immunization with OPV will no longer outweigh the burden of disease either due to paralysis caused by OPV (vaccine associated paralytic polio), or by outbreaks caused by circulating vaccine-derived polioviruses. The eventual cessation of OPV use in routine immunization programmes worldwide will become necessary to assure a lasting eradication of polio. As the world moves towards polio eradication and its certification, preparations are therefore being intensified for OPV cessation, and the risk management framework for safe OPV cessation is being put in place. The framework includes bio-containment of all known poliovirus and potentially infected substances, development of an international stockpile of oral polio vaccine, ensuring a mechanism for continued global surveillance and response for polio after eradication has been certified, and national policies if countries decide to continue vaccinating with inactivated polio vaccine (IPV). It is ironic that the vaccine on which the world has depended for polio eradication will itself become a risk to eradication once the transmission of wild poliovirus has been interrupted. Final preparations for the eventual global and simultaneous cessation of OPV will require the same level of international cooperation and coordination that has brought the world to the verge of polio eradication.     

Environmental Poliovirus Surveillance during Oral Poliovirus Vaccine and Inactivated Poliovirus Vaccine Use in Córdoba Province,Argentina

This study compares the presence of environmental poliovirus in two Argentinean populations using oral poliovirus vaccine (OPV) or inactivated poliovirus vaccine (IPV). From January 2003 to December 2005, Córdoba City used IPV in routine infant immunizations, with the exception of intermittent OPV use in August 2005. Between May 2005 and April 2006, we collected weekly wastewater samples in Córdoba City and the province''s three major towns, which continued OPV use at all times. Wastewater samples were processed and analyzed for the presence of poliovirus according to WHO guidelines. During the months of IPV use in Córdoba City, the overall proportion of poliovirus-positive samples was 19%. During an intermittent switch from IPV to OPV, this proportion increased to 100% within 2 months. During the 3 months when IPV was reintroduced to replace OPV, a substantial proportion of samples (25%) remained positive for poliovirus. In the OPV-using sites, on average, 54% of samples were poliovirus positive. Seventy-seven percent of poliovirus isolates showed at least one mutation in the VP1-encoding sequence; the maximum genetic divergence from the Sabin strain was 0.7%. Several isolates showed mutations on attenuation markers in the VP1-encoding sequence. The frequency or type of virus mutation did not differ between periods of IPV and OPV use or by virus serotypes. This study indicates that the sustained transmission of OPV viruses was limited during IPV use in a middle-income country with a temperate climate. The continued importation of poliovirus and genetic instability of vaccine strains even in the absence of sustained circulation suggest that high poliovirus vaccine coverage has to be maintained for all countries until the risk of reintroduction of either wild or vaccine-derived poliovirus is close to zero worldwide.In the context of the near achievement of poliomyelitis eradication and anticipated cessation of oral poliovirus (PV) vaccine (OPV), the World Health Organization (WHO) has recommended the use of inactivated PV vaccine (IPV) in countries that have IPV production facilities or other countries where immunization programs fulfill certain financial and logistic criteria (37). IPV has been shown to be safe and immunogenic in children in both developed and developing countries.(34) IPV diminishes the excretion of PV by children challenged with the Sabin strain of PV only moderately. The questions of whether and to which extent Sabin PV that is reintroduced into a population immunized with IPV could establish circulation, mutate to vaccine-derived PV (VDPV), and consequently cause poliomyelitis remain important. No such emergence of VDPV in developed countries using IPV has been reported. However, suboptimal hygienic conditions and insufficient vaccine coverage in middle- or low-income countries could favor the establishment of PV circulation after reintroduction, as indicated by recent VDPV outbreaks in populations with low OPV coverage (27, 38).Argentina currently uses OPV in the childhood immunization program according to recommendations from the Pan-American Health Organization. The last case of poliomyelitis due to wild-type PV was reported in Argentina in 1984 and in Córdoba Province in 1971 (24). In Córdoba City, the capital of Córdoba Province, standalone IPV (Imovax Polio; Sanofi Pasteur) replaced OPV (Polioral; Novartis Vaccines) in the routine childhood immunization program (2, 4, and 6 months of age plus a booster at 18 months age) from 1 January 2003 to 31 December 2005, while the surrounding provinces continued to use OPV. Due to an IPV shortage between 10 August and 7 September 2005, OPV was used in the capital during this period. We conducted environmental PV surveillance in Córdoba Province from May 2005 to April 2006 to describe environmental PV circulation and molecular characteristics of PV depending on the vaccine used. In the present evaluation, we also describe the dynamic of PV circulation around the change of IPV-OPV-IPV-OPV in the capital. This observation can contribute evidence regarding the dynamics of PV circulation and its implication for global immunization policy after polio eradication.     

The final stages of the global eradication of poliomyelitis

The global incidence of poliomyelitis has dropped by more than 99 per cent since the governments of the world committed to eradication in 1988. One of the three serotypes of wild poliovirus has been eradicated and the remaining two serotypes are limited to just a small number of endemic regions. However, the Global Polio Eradication Initiative (GPEI) has faced a number of challenges in eradicating the last 1 per cent of wild-virus transmission. The polio endgame has also been complicated by the recognition that vaccination with the oral poliovirus vaccine (OPV) must eventually cease because of the risk of outbreaks of vaccine-derived polioviruses. I describe the major challenges to wild poliovirus eradication, focusing on the poor immunogenicity of OPV in lower-income countries, the inherent limitations to the sensitivity and specificity of surveillance, the international spread of poliovirus and resulting outbreaks, and the potential significance of waning intestinal immunity induced by OPV. I then focus on the challenges to eradicating all polioviruses, the problem of vaccine-derived polioviruses and the risk of wild-type or vaccine-derived poliovirus re-emergence after the cessation of oral vaccination. I document the role of research in the GPEI''s response to these challenges and ultimately the feasibility of achieving a world without poliomyelitis.     

Systematic Review of Mucosal Immunity Induced by Oral and Inactivated Poliovirus Vaccines against Virus Shedding following Oral Poliovirus Challenge

Inactivated poliovirus vaccine (IPV) may be used in mass vaccination campaigns during the final stages of polio eradication. It is also likely to be adopted by many countries following the coordinated global cessation of vaccination with oral poliovirus vaccine (OPV) after eradication. The success of IPV in the control of poliomyelitis outbreaks will depend on the degree of nasopharyngeal and intestinal mucosal immunity induced against poliovirus infection. We performed a systematic review of studies published through May 2011 that recorded the prevalence of poliovirus shedding in stool samples or nasopharyngeal secretions collected 5–30 days after a “challenge” dose of OPV. Studies were combined in a meta-analysis of the odds of shedding among children vaccinated according to IPV, OPV, and combination schedules. We identified 31 studies of shedding in stool and four in nasopharyngeal samples that met the inclusion criteria. Individuals vaccinated with OPV were protected against infection and shedding of poliovirus in stool samples collected after challenge compared with unvaccinated individuals (summary odds ratio [OR] for shedding 0.13 (95% confidence interval [CI] 0.08–0.24)). In contrast, IPV provided no protection against shedding compared with unvaccinated individuals (summary OR 0.81 [95% CI 0.59–1.11]) or when given in addition to OPV, compared with individuals given OPV alone (summary OR 1.14 [95% CI 0.82–1.58]). There were insufficient studies of nasopharyngeal shedding to draw a conclusion. IPV does not induce sufficient intestinal mucosal immunity to reduce the prevalence of fecal poliovirus shedding after challenge, although there was some evidence that it can reduce the quantity of virus shed. The impact of IPV on poliovirus transmission in countries where fecal-oral spread is common is unknown but is likely to be limited compared with OPV.     

Retrospective analysis of a local cessation of vaccination against poliomyelitis: a possible scenario for the future

The global eradication of poliomyelitis will require substantial changes in immunization practices. One of the proposed scenarios includes cessation of vaccination with live oral poliovirus vaccine (OPV) and the creation of an OPV stockpile for emergency response in case of the reintroduction of poliovirus into circulation. We describe here a retrospective analysis of the cessation of OPV usage in a region of the Byelorussian Republic of the former Soviet Union in 1963 to 1966. During this period, a widespread circulation and evolution of independent lineages of vaccine-derived polioviruses took place in the region. Some of these lineages appeared to originate from OPV given to 40 children in the community during this period of essentially no vaccinations. The data demonstrate very high risks associated with both the local cessation of OPV vaccination and the proposed use of OPV to control a possible reemergence of poliovirus in the postvaccination period. The high transmissibility of OPV-derived viruses in nonimmune population, documented here, and the known existence of long-term OPV excretors should be also considered in assessing risks of the synchronized global cessation of OPV usage.     

Antigenic evolution of vaccine-derived polioviruses: changes in individual epitopes and relative stability of the overall immunological properties

The Sabin oral poliovirus vaccine (OPV) readily undergoes changes in antigenic sites upon replication in humans. Here, a set of antigenically altered descendants of the three OPV serotypes (76 isolates) was characterized to determine the driving forces behind these changes and their biological implications. The amino acid residues of OPV derivatives that lie within or close to the known antigenic sites exhibited a marked tendency to be replaced by residues characteristic of homotypic wild polioviruses, and these changes may occur very early in OPV evolution. The specific amino acid alterations nicely correlated with serotype-specific changes in the reactivity of certain individual antigenic sites, as revealed by the recently devised monoclonal antibody-based enzyme-linked immunosorbent assay. In comparison to the original vaccine, small changes, if any, in the neutralizing capacity of human or rabbit sera were observed in highly diverged vaccine polioviruses of three serotypes, in spite of strong alterations of certain epitopes. We propose that the common antigenic alterations in evolving OPV strains largely reflect attempts to eliminate fitness-decreasing mutations acquired either during the original selection of the vaccine or already present in the parental strains. Variability of individual epitopes does not appear to be primarily caused by, or lead to, a significant immune evasion, enhancing only slightly, if at all, the capacity of OPV derivatives to overcome immunity in human populations. This study reveals some important patterns of poliovirus evolution and has obvious implications for the rational design of live viral vaccines.     

Quantifying the reduction in potential health risks by determining the sensitivity of poliovirus type 1 chat strain and rotavirus SA-11 to electron beam irradiation of iceberg lettuce and spinach

Fresh produce, such as lettuce and spinach, serves as a route of food-borne illnesses. The U.S. FDA has approved the use of ionizing irradiation up to 4 kGy as a pathogen kill step for fresh-cut lettuce and spinach. The focus of this study was to determine the inactivation of poliovirus and rotavirus on lettuce and spinach when exposed to various doses of high-energy electron beam (E-beam) irradiation and to calculate the theoretical reduction in infection risks that can be achieved under different contamination scenarios and E-beam dose applications. The D(10) value (dose required to reduce virus titers by 90%) (standard error) of rotavirus on spinach and lettuce was 1.29 (± 0.64) kGy and 1.03 (± 0.05) kGy, respectively. The D(10) value (standard error) of poliovirus on spinach and lettuce was 2.35 (± 0.20) kGy and 2.32 (± 0.08) kGy, respectively. Risk assessment of data showed that if a serving (～14 g) of lettuce was contaminated with 10 PFU/g of poliovirus, E-beam irradiation at 3 kGy will reduce the risk of infection from >2 in 10 persons to approximately 6 in 100 persons. Similarly, if a serving size (～0.8 g) of spinach is contaminated with 10 PFU/g of rotavirus, E-beam irradiation at 3 kGy will reduce infection risks from >3 in 10 persons to approximately 5 in 100 persons. The results highlight the value of employing E-beam irradiation to reduce public health risks but also the critical importance of adhering to good agricultural practices that limit enteric virus contamination at the farm and in packing houses.     

Estimating the extent of vaccine-derived poliovirus infection

Background

Eight outbreaks of paralytic polio attributable to circulating vaccine-derived poliovirus (cVDPV) have highlighted the risks associated with oral poliovirus vaccine (OPV) use in areas of low vaccination coverage and poor hygiene. As the Polio Eradication Initiative enters its final stages, it is important to consider the extent to which these viruses spread under different conditions, so that appropriate strategies can be devised to prevent or respond to future cVDPV outbreaks.

Methods and Findings

This paper examines epidemiological (temporal, geographic, age, vaccine history, social group, ascertainment), and virological (type, genetic diversity, virulence) parameters in order to infer the numbers of individuals likely to have been infected in each of these cVDPV outbreaks, and in association with single acute flaccid paralysis (AFP) cases attributable to VDPVs. Although only 114 virologically-confirmed paralytic cases were identified in the eight cVDPV outbreaks, it is likely that a minimum of hundreds of thousands, and more likely several million individuals were infected during these events, and that many thousands more have been infected by VDPV lineages within outbreaks which have escaped detection.

Conclusions

Our estimates of the extent of cVDPV circulation suggest widespread transmission in some countries, as might be expected from endemic wild poliovirus transmission in these same settings. These methods for inferring extent of infection will be useful in the context of identifying future surveillance needs, planning for OPV cessation and preparing outbreak response plans.     

Complete genomic characterization of an intertypic Sabin 3/Sabin 2 capsid recombinant

The genetic properties of strain K/2002, isolated from fecal samples of a 7-month-old child who had received his first oral poliovirus vaccine (OPV) dose at the age of 3 months, are described. Preliminary sequencing characterization of isolate K/2002 revealed an S3/S2 recombination event at the 3' end of the VP1 coding region. A recombination event resulted in the introduction of six Sabin 2 amino acid residues in a Sabin 3 genomic background. Furthermore, mutations associated with loss of the attenuated phenotype of Sabin 3 strains have been identified in the genome of isolate K/2002. The data presented here emphasize the need for careful planning of vaccination strategies, which involve stopping OPV administration in regions that are certified to be polio-free.     

Evolution of the Sabin strain of type 3 poliovirus in an immunodeficient patient during the entire 637-day period of virus excretion

A 20-year-old female hypogammaglobulinemic patient received monotypic Sabin 3 vaccine in 1962. The patient excreted type 3 poliovirus for a period of 637 days without developing any symptoms of poliomyelitis, after which excretion appeared to have ceased spontaneously. The evolution of Sabin 3 throughout the entire period of virus excretion was studied by characterization of seven sequential isolates from the patient. The isolates were analyzed in terms of their antigenic properties, virulence, sensitivity for growth at high temperatures, and differences in nucleotide sequence from the Sabin type 3 vaccine. The isolates followed a main lineage of evolution with a rate of nucleotide substitution that was very similar to that estimated for wild-type poliovirus during person-to-person transmission. There was a delay in the appearance of antigenic variants compared to sequential type 3 isolates from healthy vaccines, which could be one of the possible explanations for the long-term excretion of virus from the patient. The distribution of mutations in the isolates identified regions of the virus possibly involved in adaptation for growth in the human gut and virus persistence. None of the isolates showed a full reversion of the attenuated and temperature-sensitive phenotypes of Sabin 3. Information of this sort will help in the assessment of the risk of spread of virulent polioviruses from long-term excretors and in the design of therapies to stop long-term excretion. This will make an important contribution to the decision-making process on when to stop vaccination once wild poliovirus has been eradicated.     

Combinations of Quality and Frequency of Immunization Activities to Stop and Prevent Poliovirus Transmission in the High-Risk Area of Northwest Nigeria

Background

Frequent supplemental immunization activities (SIAs) with the oral poliovirus vaccine (OPV) represent the primary strategy to interrupt poliovirus transmission in the last endemic areas.

Materials and Methods

Using a differential-equation based poliovirus transmission model tailored to high-risk areas in Nigeria, we perform one-way and multi-way sensitivity analyses to demonstrate the impact of different assumptions about routine immunization (RI) and the frequency and quality of SIAs on population immunity to transmission and persistence or emergence of circulating vaccine-derived polioviruses (cVDPVs) after OPV cessation.

Results

More trivalent OPV use remains critical to avoid serotype 2 cVDPVs. RI schedules with or without inactivated polio vaccine (IPV) could significantly improve population immunity if coverage increases well above current levels in under-vaccinated subpopulations. Similarly, the impact of SIAs on overall population immunity and cVDPV risks depends on their ability to reach under-vaccinated groups (i.e., SIA quality). Lower SIA coverage in the under-vaccinated subpopulation results in a higher frequency of SIAs needed to maintain high enough population immunity to avoid cVDPVs after OPV cessation.

Conclusions

National immunization program managers in northwest Nigeria should recognize the benefits of increasing RI and SIA quality. Sufficiently improving RI coverage and improving SIA quality will reduce the frequency of SIAs required to stop and prevent future poliovirus transmission. Better information about the incremental costs to identify and reach under-vaccinated children would help determine the optimal balance between spending to increase SIA and RI quality and spending to increase SIA frequency.     

Risks faced by laboratory workers in the AIDS era.

Laboratory workers are at occupational risk of exposure to microrganisms that cause a wide variety of diseases, from inapparent to life-threatening ones. Principal routes of transmission include percutaneous and permucosal inoculation (comprising clinical inapparent cutaneous or mucosal exposure to blood or blood products), inhalation, and ingestion. The appearance of the Acquired Immunodeficiency Syndrome (AIDS) epidemic and the first reports of occupational Human Immunodeficiency Virus (HIV) infections in health care workers resulted in high anxiety among laboratory workers. Indeed, 21% of worldwide documented cases of occupational HIV infection occurred among laboratory workers. Research laboratories pose the highest risk of infection. Safe methods for managing infectious agents ("containment") in the laboratory setting include laboratory practice and technique, safety equipment, and facility design. Infection control in the laboratory setting should take into account adherence to guidelines (biosafety levels), education and training, and the development of safety products designed to reduce the risk of exposure.