Measles virus contracted

The short answer is yes. Complications can be severe, even resulting in hospitalization or worse. Measles is less of a concern for adults, because most of them have received the MMR vaccine series. These immunizations, which protect against measles, mumps, and rubella, work incredibly well.

The first dose alone is 93 percent effective. Children who are less than a year old are naturally at a disadvantage if exposed. The recommended age for babies to receive their first vaccine is 12 to 15 months. Health experts explain that babies retain passive immunity from their mothers after birth, which can prevent them from effectively responding to vaccination. Also be aware that insurance plans may not cover the cost for babies who receive the MMR vaccine early.

Minimizing the spread of measles is relatively simple thanks to vaccines. So, why is it making such a comeback? Some travelers unknowingly contract measles while visiting another location, and then spread it once they return. Another major contributor is that some individuals have received bad information that vaccines contribute to other health issues. As a result, an alarming number of parents have chosen to skip taking their children in for the recommended MMR series.

Another factor which contributes to the communicability of measles is that an infected individual can unknowingly transmit the virus for several days before showing signs of illness. The rhinoviruses and coronaviruses, which give rise to mild common colds, are likewise transmitted by the respiratory route.

Why then do measles infections have the potential to be severe, even fatal? The answer, in part, is that the mild rhinoviruses and coronaviruses remain in the respiratory tract during infection, whereas measles virus is able to disseminate widely throughout the body.

One reason it can do so is that it can bind to several different receptors, including one called CD46, which is present on most cells of the body. Because measles virus can disseminate widely, serious complications from measles can occur in almost every organ system. Nonetheless, most measles fatalities actually result from secondary bacterial and viral infections of the respiratory and digestive tracts. These secondary infections are facilitated by a prolonged immunosuppressed state brought on by the primary measles infection.

Paradoxically, the specific immune response against the measles infection is accompanied by a not-yet-understood suppressed immune response to other new antigens. Our next and perhaps most interesting issue concerns the origin of measles virus and its establishment in the human population.

We begin this topic by first defining the contagiousness of measles virus in quantitative terms. The contagiousness of any virus is quantitatively defined by its reproduction number R0 , which is the average number of new individuals who are infected by each previously infected individual in a completely susceptible population. The R0 of measles virus is important to our analysis since, as we will see, measles virus was once an emerging virus in humans, and an emerging virus can successfully establish itself in a new host only when its R0 in that host is greater than 1.

If the R0 is less than 1, then outbreaks in the new host will be self-limiting, even if the virus emerges in the host on multiple independent occasions. What then is the R0 of measles virus in humans? The answer is 15! On the one hand, this implies that if the contemporary measles virus were to emerge in an isolated and completely susceptible human population, it would readily spread into that population. On the other hand, consider the following.

Since measles virus is so highly transmissible in humans, nearly every individual in that wholly susceptible population would be infected. Moreover, each of those infected individuals would either succumb to measles and die, or survive and develop lifelong immunity to the virus.

This creates a dilemma for measles virus. How would it be able to continually find new susceptible individuals in order to sustain itself in the population? The answer to the above dilemma is that measles virus, as it now exists, can survive only in populations that are large enough to continually generate a sufficient number of new susceptible individuals. Mathematical modeling by epidemiologists has led to the estimate that a community of at least , persons is necessary to sustain measles virus.

This leads to the somewhat astonishing conclusion that measles virus, as we know it, has existed in the human population for no longer than the last several millennia, since communities large enough to sustain measles virus did not exist before then, and the much smaller communities that did exist had only occasional contact with other human groups. The above line of argument also explains why, in the pre-vaccine era, measles outbreaks or epidemics occurred every several years, with many fewer cases occurring between epidemics.

Moreover, it leads to the notion that epidemic diseases in humans are a relatively recent development. To these points, consider the following. Measles virus shares the following three essential features with other epidemic viruses e. First, each of these viruses is highly contagious, such that each spreads quickly through the susceptible individuals in the population.

Second, epidemic viruses give rise to acute infections. Third, epidemic human viruses have no animal reservoir to sustain them. At the end of an epidemic, the virus persists in the human population, but only at a low incidence, and only if the population is large enough. Then, as a sufficient number of new susceptible individuals are born into the population, the epidemic threshold is reached, and the cycle repeats.

The above argument also explains why very young children are the targets of epidemic viruses; they are the only non-immune individuals in the population. Since measles virus, as it now exists, only recently became established in the human population, and since measles virus has no known animal reservoir, where did it come from?

MV infection stimulates the expression and activation of the leukocyte integrins lymphocyte function associated antigen-1 and very late activation antigen-4 [ 47 ]. These molecules allow adherence of infected migrating cells to the endothelial cells and subsequent trans-migration into the tissues [ 46 , 47 ].

Infection of endothelial cells with MV in vitro stimulates the production of colony-stimulating factor and thus increases the adhesion of granulocytes to infected epithelial cells [ 48 ].

MV antigens were found in the capillary endothelium of lymph nodes and thymus in patients who died from the infection [ 49 ]. MV can also infect permissive cells through receptor-independent mechanisms [ 50 ], although these mechanisms are much less efficient than receptor-mediated entry.

One of the possible mechanisms is through an in-cell infection. This mechanism has been identified in allowing Epstein-Barr virus EBV spread from infected B-cells to epithelial cells by internalisation of the EBV-infected B-cells into carcinoma cells, resulting in activation and transfer of the virus to the carcinoma cells in vitro and in vivo [ 51 ].

It is tempting to speculate that MV-infected lymphocytes can also be internalised by receptor-negative cells, leading to infection. The rash can potentially be explained by infection of the dermal endothelial cells and keratinocytes, which are subsequently cleared by the virus-specific host cellular immune response [ 3 ]. Several studies reported that viral antigens were found in the corneal layer, spongiotic epidermal keratinocytes and even more in the dermal papillary layer [ 15 ].

The skin lesions were characterised with spongiosis, cell necrosis and mononuclear cell infiltration of the epidermal keratinocytes [ 14 , 15 ]. The crucial role of the host immune response in the pathogenesis of the skin rash is illustrated by the fact that immunocompromised patients often do not develop skin rash following MV infection, although the course of a MV infection in these patients is typically severe and can be lethal [ 53 ].

Although most measles cases resolve without complications, the virus can remain persistent and infect the CNS on rare occasions. The disease is hallmarked by demyelination, which results in ataxia, motor and sensory loss and mental status changes [ 56 ] and can result in death.

The risk of developing MIBE increases when the MV infection occurs in young infants or immunocompromised individuals, who are unable to clear the infection.

The symptoms of MIBE often include mental status changes, focal seizures and occasionally visual or hearing loss within one year of acute measles infection or live-virus vaccination [ 57 , 58 ]. The disease progresses rapidly to coma and death in the majority of patients [ 54 ]. A third and very rare neurological complication of measles is SSPE.

Symptoms develop several years after a normal episode of measles and usually start with a decline of school performance and a slight change of behaviour, progressively followed by myoclonic seizures, ataxia and death within one to three years [ 25 , 59 ]. SSPE is exclusively associated with infections with wild-type MV, and has never been observed in association with genotype A vaccine viruses.

Where the virus persists and how it spreads in the CNS remains unknown. It has been suggested that the virus spreads from one neuron to the other through interconnecting processes in vitro and in vivo, without the release of infectious particles [ 60 , 61 , 62 ]. This infection may rely on membrane fusion between infected and uninfected neurons, allowing trans-synaptic transmission of ribonucleoprotein RNP [ 25 , 63 , 64 ]. The RNP consists of genomic viral RNA encapsidated with the viral nucleoprotein and associated with the viral polymerase, and is the minimal unit of infection [ 3 ].

The virus may spread from one glial cell to another via interconnected processes [ 25 ]. It is still unclear how MV enters the CNS, however in recent years it has become apparent that the blood-brain-barrier allows entry of lymphocytes into the brain [ 65 , 66 ].

Moreover, it has been shown that the brain even contains lymphatic vessels [ 67 ]. Therefore, infected lymphocytes circulating in peripheral blood during viremia could carry the virus into the CNS, where the virus could be transmitted via a yet unknown cellular entry receptor or receptor-independent entry mechanisms. The basic reproductive number R 0 reflects the average number of secondary cases that would arise when an infectious agent is introduced into a completely susceptible population [ 68 ].

MV is released into the air as cell-free or cell-associated virus particles, predominantly by coughing [ 9 , 10 , 69 ]. The virus is highly infectious: the estimated R 0 is 12 to 18 [ 68 ]. The high infectivity of MV can be attributed to three crucial transmission properties. First, measles patients must efficiently shed MV. Tracheo-bronchial epithelial cells have been reported to be susceptible to MV infection [ 10 , 25 , 43 , 44 ], associated with epithelial damage in the bronchi and bronchioles [ 27 , 43 ].

Whereas epithelial cells are infected from the basolateral side, budding occurs exclusively at the apical cell surface due to sorting signals in the viral glycoproteins.

Hence, virions remain in the mucus as cell-free particles, and are moved to the upper respiratory tract URT by the mucocilliary escalator [ 43 ] and discharged into the environment by coughing. MV can be transmitted by large respiratory droplets by direct contact or in small aerosols transported through the air over long distances [ 72 ].

The release of new MV particles from the host into the air is illustrated in Figure 3. The third stage of MV infection: transmission of new MV particles via the air. Epithelial damage in infected lymphoid tissues, such as the tonsils A , releases virus particles produced by lymphocytes into the upper respiratory tract B. Epithelial damage in the lower respiratory tract induces cough panels C and D , enhancing the discharge of aerosols containing MV particles.

Second, the virus must remain infectious until it reaches a new host. Large droplets may increase the stability of cell-bound MV particles or cell debris that are expelled from the body, allowing the virus to survive long enough until it comes into contact with the eyes, nose or mouth of a susceptible person.

Alternatively, cell-free virions transmitted airborne as small aerosols through a turbulent airflow may survive in air for at least one hour, as demonstrated during the outbreaks of measles in a paediatric practice in and at an International Special Olympics Games in [ 72 , 73 ].

The last vital transmission property concerns the infectious dose of the virus. However, measles patients shed large amounts of virus, resulting in transmission of numerous infectious units. The combination of large inoculum and low infectious dose may increase the chance of rapid deposition of virus particles in the respiratory tract of the next host, especially in a crowded and poorly ventilated environment [ 73 ].

MV infection results in a transient and profound immune suppression, which leads to increased susceptibility to opportunistic infections and increased childhood mortality [ 4 ]. The virus efficiently replicates in lymphoid tissues. Tertiary lymphoid tissues, such as BALT and gut associated lymphoid tissues GALT , can be induced by bacterial or viral infection that leads to the accumulation and proliferation of lymphocytes and the formation of germinal centres.

Since BALT and GALT are known to enhance protective immunity against mucosal pathogens, obliteration of these lymphoid tissues that are present in major entry portals for opportunistic infections the airways and gut can facilitate infiltration of the mucosa by previously encountered viruses or bacteria. MV infection leads to lymphopenia during its acute phase, in which the number of T- and B-cells, both circulating and lymphoid tissue homing, decreases extensively Figure 2 C [ 27 , 78 ].

Peak numbers of MV-infected cells in lymphoid tissues of experimentally infected NHPs coincide with the peak of viremia, rapidly followed by B-cell exhaustion in the germinal centres [ 27 ], as previously also reported in humans [ 38 ].

The infection induces an expansive effector phase, leading to the clearance of MV-infected cells by cytotoxic T-cells [ 79 ] and subsequently a lifelong measles-specific immune response [ 80 ]. Following viral clearance, the number of lymphocytes returns to normal within approximately one week. However, while the lymphopenia lasts for a week, the immune suppression may last variably from several weeks to up to more than two years [ 4 ].

This led to the initial dismissal of the role of immune cell depletion in causing measles-induced immune suppression [ 81 ]. Instead, functional impairment of the immune cells has often been proposed to explain the mechanism of the immune suppression. However, there is limited evidence that this is the case and it has proven difficult to identify a cell surface receptor that mediates suppression of proliferation in immune cells.

Reduced proliferative responsiveness of peripheral blood lymphocytes to antigenic or mitogenic stimulation has also been suggested as a mechanism of measles immune suppression. Although this impairment is indeed detected in vitro, measles is associated with dramatic levels of lymphoproliferation in vivo [ 27 ]. Other mechanisms have been proposed to explain the nature of the measles-induced immune suppression, such as altered cytokine profiles [ 82 , 83 , 84 , 85 ] or inhibited haematopoiesis [ 86 , 87 ], but none of these fit with the measles paradox: Prolonged increased susceptibility to infectious disease and coinciding induction of strong MV-specific immune responses.

The loss of memory lymphocytes is masked by a massive expansion of new MV-specific and bystander lymphocytes, explaining the short duration of lymphopenia and yet the long duration of immune suppression. This finding thus revives the importance of immune cell depletion as a key mechanism for measles-associated immune suppression. Mechanisms underlying MV entry, dissemination, transmission and immune suppression as discussed in this review are illustrated with images from experimentally infected NHPs in Figure 4.

Measles has caused a high number of fatalities throughout history. Recombinant viruses expressing fluorescent reporter proteins have given us the means to study and understand the virus and its pathogenesis from a new perspective. However, these advances not only leave some old mysteries concerning measles pathogenesis unexplained, but also give birth to new questions.

Since global eradication of measles is planned for the near future, studies on MV tropism and pathogenesis not only remain important, but also become urgent [ 89 ]. Brigitta M. National Center for Biotechnology Information , U. Journal List Viruses v. Published online Jul Laksono , 1 Rory D. Paul Duprex , 3 and Rik L. Find articles by Brigitta M. Rory D. Find articles by Rory D. Paul Duprex. Rik L. Find articles by Rik L. Richard K.

Plemper, Academic Editor. Author information Article notes Copyright and License information Disclaimer. Received Jun 2; Accepted Jul This article has been cited by other articles in PMC. Abstract Measles virus is a highly contagious negative strand RNA virus that is transmitted via the respiratory route and causes systemic disease in previously unexposed humans and non-human primates.

Keywords: measles virus, immune suppression, pathogenesis, tropism, transmission. Introduction Measles virus MV is the prototype member of the genus Morbillivirus, the subfamily Paramyxovirinae and the family Paramyxoviridae. Entry Respiratory epithelial cells have classically been considered as the early target cells of MV infection in the respiratory tract.

Open in a separate window. Figure 1. Dissemination Primary bone marrow and thymus , secondary spleen, tonsils, lymph nodes and tertiary e. Figure 2. Transmission The basic reproductive number R 0 reflects the average number of secondary cases that would arise when an infectious agent is introduced into a completely susceptible population [ 68 ]. Figure 3. Immune Suppression MV infection results in a transient and profound immune suppression, which leads to increased susceptibility to opportunistic infections and increased childhood mortality [ 4 ].

Figure 4. Conclusions Measles has caused a high number of fatalities throughout history. Acknowledgments Brigitta M. Conflicts of Interest The authors declare no conflict of interest. References 1. De Vries R. Morbillivirus infections: An introduction.