Immune Containment and Consequences of Measles Virus Infection in Healthy and Immunocompromised Individuals

Abstract

2The pathogenicity of measles virus (MV) is intimately linked to the immune status of the infected individual. Measles is typically a self-limiting disease; however, individuals who are immunocompromised (56,79), malnourished (26,78,113), or at the extremes of age (23) are at increased risk for severe measles. At the present time, with human immunodeficiency virus (HIV) and immunosuppressive drug therapy affecting the immune competence of large numbers of individuals, MV is reemerging as an important pathogen worldwide. Elucidating the mechanism by which the immune system controls MV infection and prevents reinfection will be crucial for our understanding of disease pathogenesis and transmission as well as the development of novel MV vaccination strategies.Despite reaching global measles vaccination coverage of Ͼ80% of individuals, MV remains the fifth leading cause of death and the most common cause of vaccine-preventable death in children under 5 years of age (84). An estimated 31 million cases of measles occurred globally in 2001, resulting in 777,000 deaths, the majority (452,000) of which occurred in sub-Saharan Africa (84). MV is one of the most contagious pathogens known to humans, and large measles outbreaks, facilitated by overcrowding in poor communities, continue to occur even in countries that have achieved high vaccine coverage.MV is a 15-kilobase, enveloped, negative-strand RNA virus and a member of the Morbillivirus genus of the Paramyxoviridae family. MV infects only humans and nonhuman primates. It is a stable, monotypic virus, making it an excellent candidate for eventual eradication. In culture, MV can be adapted to grow in nonprimate cells, a process that has facilitated the attenuation of viral strains for the development of a safe vaccine. Measles is transmitted via direct person-to-person contact and causes a symptomatic viral prodrome culminating in the hallmark maculopapular measles rash. The measles rash is preceded by systemic viremia and lymphopenia, and clearance of the rash is followed by a transient suppression of T-lymphocyte responses that lasts several weeks, leaving the infected individual susceptible to other infections.While nonspecific innate immune mechanisms may be important in the control of MV during the first days following infection, adaptive MV-specific immune responses mediate viral clearance and provide protection against subsequent MV infections. Natural MV infection generates long-lasting immunity that includes both MV-specific antibody (14) and memory T-lymphocyte (50, 123, 136) responses. Long-term protection from reinfection occurs without a requirement for reexposure (98).This article reviews our current understanding of the immune control of MV and the consequences of MV infection on the immune system of the immunocompetent host. We then discuss the clinical consequences of MV infection in immunocompromised individuals. Finally, we describe recent studies that have raised questions regarding the outcome of MV infection in the immunocompromised host. IMMUNE CO...

Implications of vaccination and waning immunity

“…It is found that the within-host model agrees well with the observed pathogenesis of measles infection and vaccination (Heffernan & Keeling 2008). It has been observed that the pathogenicity of measles virus is intimately linked to the immune status of the infected individual (Permar et al 2006). Equation (3.1) replicates this result; in particular, the level of immune memory, m, determines whether the ensuing infection is symptomatic or asymptomatic, as well as controlling the subsequent level of transmission, the duration of infection and the degree of immune boosting (see Heffernan & Keeling (2008) and the electronic supplementary material for details).…”

Silent casualties from the measles outbreak in South Africa

“…All patients were HIV-positive and, with one exception, had CD4 counts <100 cells/µl at the time of measles infection, consistent with SME as an opportunistic infection in an immunocompromised host. 4 The measles virus enters the CNS with the initial viraemia, but it is thought that a poor cell-mediated immune response allows virus to persist in this compartment with the potential for SME. 4 Interestingly, the 2 survivors were those with the least compromised CD4 counts; one had reconstituted on ART and the other was the least affected clinically.…”

“…4 The measles virus enters the CNS with the initial viraemia, but it is thought that a poor cell-mediated immune response allows virus to persist in this compartment with the potential for SME. 4 Interestingly, the 2 survivors were those with the least compromised CD4 counts; one had reconstituted on ART and the other was the least affected clinically. In immunosuppressed animals infected with the measles virus, the repopulation of lymphocytes was associated with the elimination of viraemia, 4 suggesting that immune reconstitution in HIV-infected patients may enable a more robust immune response.…”

“…4 Interestingly, the 2 survivors were those with the least compromised CD4 counts; one had reconstituted on ART and the other was the least affected clinically. In immunosuppressed animals infected with the measles virus, the repopulation of lymphocytes was associated with the elimination of viraemia, 4 suggesting that immune reconstitution in HIV-infected patients may enable a more robust immune response. Furthermore, human leukocyte antigen (HLA) polymorphisms influence measles antibody responses, which may be a modifying factor influencing susceptibility to this measles complication.…”

“…There are 2 further rare and latent CNS complications resulting from a preceding measles infection: subacute sclerosing panencephalitis (SSPE) caused by years of viral persistence in a seemingly immunocompetent host, 3 and subacute measles encephalitis (SME), occurring in an immunocompromised host. 4 SME manifests 1 -7 months after the acute measles infection. 5 Patients present with seizures, often epilepsy partialis continua, and altered mental status.…”