Considerations for Viral Disease Eradication Lessons Learned and Future Strategies: Workshop Summary (2002) / Chapter Skim
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3 Biological Challenges to Post-Eradication
3 Biological Challenges to Post-Eradication
Pages 64-97
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From page 64... ...
Mathematical modeling that takes these interactions into account provides a robust scientific framework for predicting the impact of mass vaccination and exploring immunization cessation strategies. It can help us answer questions such as: How extensive must vaccination be to interrupt transmission in a clefined population?
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From page 65... ...
Department of Infectious Disease Epidemiology Imperial College School of Medicine University of London, London, U.K. The past four decades have witnessed remarkable success in the control of viral diseases by mass vaccination.
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From page 66... ...
processes, such as the demography of the human host, human behavior, and the biological factors that influence transmission all play critical roles in determining the impact of mass vaccination. The dynamics of the interaction between an infectious agent and its human host population are complex and often highly non-linear in form due to variation in the course of infection within the human host and the interaction of demography (e.g., net birth rate)
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From page 67... ...
/[A - M] , where L is human life expectancy, M is the average duration of protection from maternally derived antibodies, ancI A is the average age of infection in an unvaccinated community.
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From page 68... ...
documented in Figure 3-1. The pattern displayed provides considerable information relevant to the design of mass vaccination programs.
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From page 69... ...
Mass Vaccination Theory also sheds light on the degree of mass immunization required to block transmission in a defined population. If the average age at immunization is V, and A and L are as defined previously, then the critical proportion of each yearly birth cohort that must be effectively immunized to block transmission, Pc' is given by the simple expression (Anderson and May, 19921: Pc = ILL - AJ/tA _ Ad.
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From page 70... ...
An average age at infection of around one to two years prior to mass vaccination requires that immunization be effectively administered near birth in order to block transmission. However, if delivered too soon after birth, the presence of maternally derived antibodies significantly reduces vaccine efficacy.
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From page 71... ...
Second, immunization tends to lengthen the inter-epidemic period. Third, a trough of susceptibility moves across the herd immunity profile in older age classes, due to decreased transmission rates and exposure following the mass immunization (see Figure 3-3~.
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From page 72... ...
Catch-up campaigns are especially valuable in developed countries, where they serve to mop up susceptible pockets within the population. However, it is important to recognize that any cessation or decline in effectiveness of either cohort or pulse programs will rapidly lead to a buildup of susceptibles, particularly in high birth rate communities.
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From page 73... ...
First, successful programs tend to increase the average age of infection. Consequently, cases of infection are often observed in clusters in older age classes (i.e., older than the age class for which immunization is first offered>.
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From page 74... ...
The magnitude of these indirect benefits increases rapidly as overall vaccine coverage increases and, as illustrated in Figure 3-5, may comprise a significant fraction of the overall benefit. The magnitude of the indirect benefit is calculated in a way that takes into account the impact of immunization on transmission success as a function of vaccination coverage.
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From page 75... ...
For example, in the United Kingdom, in the past few years unfounded reports of an association between MMR vaccination and autism in children has resulted in a significant decline in vaccine uptake in the last two years. The spurious correlation arises from the fact that the average age of onset of autism prior to wide-scale immunization was around two years of age, which is also the current average age at first immunization.
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From page 76... ...
In contrast, smallpox had a high average age of infection prior to wide-scale vaccination, even in densely populated areas, and was much less transmissible than either polio or measles (Fenner et al., 19881. In developed countries, mass vaccination will probably have to be maintained at very high levels for quite a while in order to protect against reintroductions from areas where poverty, human conflict, or absence of political will impedes high coverage.
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From page 77... ...
Professor, Departments of Pathology and Microbiology and Immunology University of Texas Medical Branch, Galveston, TX The interruption of viral transmission associated with viral disease eradication requires a high vaccination coverage of the human population, a vaccine that eliminates transmission in a certain region for the duration of intensive immunization, and an effective assay for the virus and its antibodies. The biological basis of these requirements necessitates a thorough understanding of the viruses being targeted for eradication.
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From page 78... ...
Successful longdistance introductions seem to involve vectors that are very adaptable and readily transportable (e.g., Aedes aegypti and Culex pipiens) , or viruses (e.g., Venezuelan equine encephalitis and Rift Valley fever virus)
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From page 79... ...
We are entering an era in which small viral genomes can be synthesized and converted to infectious agents. Soon, even larger viruses will likely be synthesized from sequence information or clones.
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From page 80... ...
In the case of poliovirus, for example, control would probably be impossible with the Salk vaccine because it is not known to reliably interrupt transmission and control with the Sabin vaccine would expose the borders of the vaccinated groups to partially reverted virus transmission. A subunit or vectored vaccine with mucosal efficacy would be invaluable; it would prevent the risk of reversion to virulence associated with attenuated vaccines, and it would eliminate the possibility of residual live virus being present in inactivated vaccines (a known problem for several viruses, including poliovirus and the animal foot and mouth disease virus)
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From page 81... ...
Many feel it is not worth arguing over elimination of a virus that only spreads among humans and has severe adverse health effects. If an infectious virus does go extinct but information is still needed that requires a viral genome or even a live virus, viral genes could readily be synthesized from nucleic acid sequences.
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From page 82... ...
BSL-3 is used for highly aerosolinfectious agents that cause human disease. For example, {ymphocytic choriomeningitis virus is classified as BSL-3 because of its capability to efficiently infect the laboratory worker with low concentrations of small particle aerosols.
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From page 83... ...
Reconstitution of poliovirus, release of hidden stocks of smallpox virus, and other mischief are all possible. Although they would limit the damage, precautions may not completely protect us (particularly against blackmail)
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From page 84... ...
infection has been reported for 26 different species of African non-human primates. Two of these viruses, SIVcpz from chimpanzees and SIVsm from sooty mangabeys, have crossed the species barrier to humans on multiple occasions, generating human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2)
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From page 85... ...
This highlights the potential significance of even a single primate lentiviral transmission from primates to humans and illustrates the importance of surveillance of human and primate populations for novel SIV infections. African primates represent an extremely large reservoir of lentiviruses with the potential for infecting other species, including humans.
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From page 86... ...
Phylogenetic analyses have shown that all viruses from any one simian species are generally much more closely related to each other than to viruses from other species (Hahn et al., 2000~. SIV transfers between different primate species in the wild have been documented; however, the frequency of such transmission events, the clinical outcomes, and the factors required for establishing new primate lentiviral infections are unknown.
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From page 87... ...
Together, these findings provide compelling evidence that HIV-1 arose as a consequence of three independent SIVcpz transmissions from naturally infected chimpanzees in west central Africa. Although the routes and circumstances of cross-species transmissions are unknown, it is believed that human infection with SIVcpz and SIVsm resulted from exposure to infected blood during the hunting and field dressing of animals, the preparation of primate meat for consumption, and bites and scratches from infected pets or wounded animals (Hahn et al., 2000~.
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From page 88... ...
In each case, mosaic viruses comprised of different SIV lineages are widely distributed in their respective host species and thus represent cases where cross-species transmission and recombination have led to successful virus adaptation and dissemination, perhaps even outcompeting the previous incumbent SIVs. As the prevalence rates of HIV-1 group M viruses are rising in west central Africa, recombination of newly introduced SIVs with circulating HIVs has become a more probable scenario.
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From page 89... ...
Characterize the origins and evolutionary history of the entire group of primate Determine to what extent humans are exposed to SIV and whether such exposure has led to additional zoonotic transmissions: · Develop novel screening and confirmatory assays that can detect and distinguish the wide variety of SIV infections now known to exist in wild primate populations. · Establish effective surveillance mechanisms for humans at risk for zoonotic .
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From page 90... ...
Because experimental HIV vaccines will eventually be tested in countries worldwide, the occurrence of new zoonotic SIV infections and their possible impact on immunization efforts will need to be examined. The existence of a primate reservoir must be taken into account while planning future eradication strategies for HIV/AIDS.
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From page 91... ...
Recently, two antibody-deficient patients with VAPP shed virus in their stool for over five years after their last vaccination. Comparison of the sequence of these viruses with that of OPV suggests that
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From page 92... ...
These neurovirulent strains of OPV were not associated with VAPP in either of these two studies. In Poland, from March to December 1968, there was an outbreak of poliovirus type 3 four months after vaccination with a live attenuated OPV3, USOL virus.
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From page 93... ...
Like the Caribbean epidemic, vaccination coverage was low in Egypt cluring this time, anct circulation of OPV-derivect virus stopped when vaccine coverage increased. From March to fuly 2001, 3 cases of cVDPV occurred in the Philippines.
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From page 94... ...
Genetic characterization of new West African simian immunodeficiency virus SIVsm: geographic clustering of household-derived SIV strains with human immunodeficiency virus type 2 subtypes and genetically diverse viruses from a single feral sooty mangabey troop. Journal of Virology 70:3617-3627.
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From page 95... ...
2000. Env sequences of simian immunodeficiency viruses from chimpanzees in Cameroon are strongly related to those of human immunodeficiency virus group N from the same geographic area.
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From page 96... ...
2001. Ongoing exposure of humans to simian immunodeficiency viruses in West Central Africa poses a risk for additional zoonotic transmissions.
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From page 97... ...
1998. Simian immunodeficiency viruses (SIVs)
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