Who discovered mumps virus

In total, there have been 25 deaths in Europe, of which 22 occurred in Romania. Portugal, Switzerland, and Bulgaria also had measles fatalities. The ECDC is exploring national Immunization Information Systems to improve the monitoring of immunization coverage at local geographical levels, linking individual immunization histories with health outcome data for vaccine safety, effectiveness, as well as failures, and educational material for vaccine researchers, producers, providers, and recipients.

Imported and secondary measles cases appeared in California in , a state that allowed personal beliefs exemptions to easily override laws requiring full immunization such as two doses of MMR vaccine for all children and young adults attending schools. This led to extremely low MMR vaccination rates at some schools, particularly private schools, with even zero coverage in some kindergartens.

The outbreak led to changes in Californian law requiring parents to consult with the local public health office and requiring a medical certificate stating medical reasons for exemption. This process will make it more difficult for parents to deny this immunization to their children, which puts all unimmunized children at risk due to the highly infectious nature of measles.

The new immunization requirement in California has resulted in increased coverage of MMR and other vaccines to over 95 percent. The science behind vaccine development has increased its capacity markedly in recent years with genetics and immunology entering new spheres of research for vaccines to combat cancers and genetic diseases, which is expected to play a major role in clinical medicine and public health in the coming decades.

The cases of measles and hepatitis B are prime examples of vaccines that have been developed in partnership with many contributing laboratories, manufacturers and public health leaders with shared information and scientific advances leading to reduced global mortality rates.

Scientists and manufacturers worked together to create the HBV vaccine produced by using one element of the cellular wall of the virus instead of the whole virus, increasing the safety of the vaccine. Hilleman later developed the first immunizations with recombinant vaccines, contributing to the application of advances in genetic sciences for vaccinology in the future to provide low-cost and widely effective new approaches to vaccination.

Public trust in vaccines has become an important global health issue, with negative attitudes due to fears over false but highly publicized side-effects and hesitancy among some doctors. Italy and Germany are making vaccination mandatory after health officials warned that a fall-off in vaccination rates had triggered a measles epidemic.

In 10 European countries, cases of measles doubled in number in the first two months of compared to , as reported by the ECDC, with more than 2, cases in , almost ten times the number in Notwithstanding the astonishing success of vaccines in saving millions of lives and promoting civil societies, vaccine development, production, and implementation have many ethical issues and controversies.

These range from ideological anti-vaccinatonism, to professional jealousies and controversies, along with economic and legal disputes over cell lines for vaccine production, to allegations of vaccines causing diseases in children, slow adoption of life-saving vaccines, inadequate resource allocation in developing countries, lack of harmonization of vaccination policies, and others.

Recently, rates of parental refusals of vaccination have increased. This is due, in part, to increased public skepticism of public health professionals, policymakers, and the pharmaceutical industry.

Reduced public health awareness is also due to the successful control and near-elimination of many once dreaded infectious diseases such as smallpox and poliomyelitis. Today, most parents, health care staff and doctors have never seen the diseases prevented by vaccines and do not understand their gravity.

Public anxiety surrounding vaccinations rose in the United Kingdom in the s in response to concerns about the safety of the pertussis vaccine.

This resulted in a decline of immunization coverage and the return of this once well controlled disease. In the mid - s UK uptake of MMR vaccination fell from a peak of 92 percent at the age of two to 82 percent in , with uptake falling below 75 percent in parts of London. This has serious implications for mutual protection of the population, i. The harm created by publication of fraudulent and unethical research activities has had an adverse impact on professional and public perception of matters such as vaccines.

In , an article published in Lancet by Andrew Wakefield purported to show that the measles—mumps—rubella MMR vaccine caused autism. This created a storm of public concern and parental refusals of the MMR vaccine. Media investigation and professional studies proved the study was fabricated, and many reliable studies have since disproved its claims. However, despite the media coverage and retraction of the article, the credibility of vaccinations—specifically MMR vaccine—in the eyes of the public was damaged substantially.

The allegation, although proven to have been fabricated, continues to be widely believed and spread via the internet and social media. Popular resistance to vaccination is both a legal and ethical question as reflected in current controversies in the United States, where opting out of mandatory vaccination has contributed to measles outbreaks, a disease that was considered eradicated many years ago. All 50 US states have legislation requiring specified vaccines for students.

However, exemptions are allowed for medical reasons, and for reasons of religious beliefs and 18 states allow philosophical exemptions for those who object to immunizations because of personal, moral, or other beliefs National Conference of State Legislatures, Pediatricians in the United States are reporting increased refusal of parents to immunize their children, prompting the American Academy of Pediatrics AAP , the American Medical Association AMA and the American College of Physicians to recommend the elimination of non-medical exemptions in state immunization laws.

Refusal of vaccination can be seen as posing a threat to other children, as well as a form of child neglect such as having a child in a car without an appropriate child car seat. In part, this action is stimulated by concern over increasing resistance of parents to vaccination along with return of previously controlled diseases.

Failure to vaccinate is a form of child neglect. Both the public and private sectors, including the pharmaceutical industry, have contributed greatly to increasing vaccine coverage rates, and public—private partnerships remain vital to vaccinology. As a senior staff member of Merck, responsible for vaccine development at a major pharmaceutical company, Hilleman conducted industry-funded research and his contribution led directly to manufacture of the majority of vaccines created in the latter half of the 20 th century that have been, and remain, vital for public health in the US and globally.

The role of the private pharmaceutical industry needs to be recognized as crucial for advances in this field, but is equally dependant on scientists at universities and public research institutions with their contribution to the knowledge base that enabled breakthroughs in vaccine production and distribution.

The Zika virus transmitted to a pregnant woman by Anopheles mosquitoes, or by sexual relations with a Zika infected partner may produce a mild illness. The race to develop effective vaccines must involve public—private cooperation to achieve a working vaccine within several years. The long time gap from availability and proof of vaccine success until it is adopted globally is an ethical issue for reducing global health inequities as well as a question of priorities and resource allocation in public health.

Adoption and implementation of vaccination is slow to respond to important advances, especially in low-income countries where policy-makers have traditionally given health low priority in governmental financing.

Delays in vaccine adoption lead to preventable infections, with high rates of illness, deaths, human misery, and slowing of economic progress. Lack of harmonization of vaccination policies is a major professional, public policy, ethical issue and a limiting factor in achieving the full potential of proven successful and safe vaccines.

Europe, and the European Union, still does not have a common harmonized immunization program, in some cases not even in the same country, which contributed to the massive measles epidemics since The benefits to society of vaccination are enormous, not only in saving lives and reducing morbidity, but also in reduced health care costs.

Vaccines are life-saving and cost-effective, and they should be supported by national governments and international donor programs alongside the buildup of public health education and infrastructure development within recipient countries. Vaccines have been crucial in reducing child illness and birth defects —e.

Vaccines help men, women and especially children to have healthy lives without morbidity of many previously common childhood diseases e. They also lessen infections among people with chronic medical and disabling conditions such as pneumococcal pneumonia and influenza vaccines. Reducing disease and high mortality rates promotes economic growth as supported by the World Bank and other economic analyses. Successful vaccination also increases equity in society by reducing diseases that were often more common among poorer populations.

Since , the World Bank and economic analysts have accepted that the economic benefit to low- and medium-income countries LMICs of reducing child mortality—mostly resulting from reduced morbidity and mortality from infectious diseases—is vital to their economic and social advancement. Nearly universal use of hepatitis B vaccine for newborns has helped to prevent mother-to-child transmission and subsequent prevention of liver cirrhosis and liver cancer, which is of enormous economic value to health systems.

The vaccine to prevent the spread of hepatitis A is available and used in many countries, but a vaccine for the more serious disease of Hepatitis C has regrettably not yet been developed.

Although effective, life-saving treatments are available, these are costly and an effective vaccine would bring greater benefits and advances. A review of cost effectiveness and economic benefit studies of vaccines in LMICs concluded that vaccination brings important economic benefits and recommends that policy-makers should consider vaccines to be an efficient investment.

Immunization averts an estimated two to three million deaths every year from diphtheria, tetanus, pertussis whooping cough , and measles. However, an additional 1. Since its founding in , GAVI helps finance adoption of vaccines in low-income countries dependent on external support to finance vaccination. The percentage of low-income countries financing vaccines in their national budgets rose from 64 percent in to 75 percent in , with a modest increase in national government share of routine immunization rising from 35 percent to 39 percent between and A study reviewed publications from 27 countries which introduced rotavirus vaccine into their national routine immunization programs since Measles is a highly contagious and potentially fatal disease which is a leading cause of death among young children see Box Efforts to control, eliminate, and ultimately eradicate measles are part of international organizations and WHO strategy.

An economic analysis by Levin et al. In recent years, many cost-effectiveness studies of vaccines for hepatitis B, rotavirus, human papilloma virus, and influenza have shown that vaccination is an effective economic tool with significant health benefits.

Global targeting of rubella for eradication along with measles for achievement by will require new tactics in Europe, such as harmonization of immunization programs across the region, and certainly in the European Union where there is free border crossing between member states and large-scale refugee entry without evidence of past immunization. The tools exist in outstanding vaccine combinations, especially the MMR vaccine created by Hilleman.

Measles and rubella control—and ultimately eradication—are within the capacity of well-led public health policy and resources see Box The sciences of vaccinology depend on academic research and on the private sector of the limited number of vaccine producers in the world. Long known diseases such as malaria, HIV, TB, dengue, West Nile fever and others are also part of the urgent call for new vaccines challenging the research capacity of academia and private manufacturers.

The process of discovery is only part of a long and costly process of initial testing of safety and efficacy. New institutional and funding arrangements will be needed to make the most of new technology and genetics in vaccine development for these and new challenges that may be expected to arise.

Vaccine development and distribution have saved millions of lives, and have the potential to save millions more as new vaccines emerge from public and private research centers, through the pioneering achievements of the next generations of Hilleman and colleagues.

Policy-makers in public health systems will continue to improve vaccine delivery and to implement vaccination programs for reduced morbidity and mortality rates across the globe. Vaccines are among the most efficient preventive measures available to both clinical medicine and public health. However gains from successful immunization campaigns are being rolled back as rates of vaccine refusal increase.

Public support can be won or eroded by pro- and contra-advocacy groups. Public concerns over vaccine safety can become wildly exaggerated and has the effect of reducing vaccine acceptance. The support of medical practitioners and the media is vital to promote adoption and acceptance of newer vaccines by an often skeptical public. Neither the science, nor the application of its advances, occur automatically.

Hilleman believed and demonstrated that academic and industry-based scientists could work in a complementary fashion in support of global public health goals for disease control and eradication, as vaccine development and distribution have a crucial role in population health.

The prospects look favorable for scientific advances leading to new vaccines and to the potential for further disease control and eradication. This process requires long and expensive periods of basic sciences research and vaccine testing, and when proven effective and safe, the implementation of immunization programs.

In many countries, adoption of new vaccines in routine immunization programs has proven to be slow. Disease control depends on monitoring case reports including quantity, common factors such as time, location, risk factors, and available intervention that can be applied to control epidemic or endemic diseases. It is essential to reach out to especially vulnerable groups living in urban poverty areas as well as remote villages and those with particular risk factors for diseases.

This is the context in which vaccines are of enormous social and economic benefit, as well as being critical to improve health, prevent disease, and avoidable mortality. A well-trained public workforce is required to meet these challenges. Ultimately, ensuring the development of these key preventive measures to reduce—and in some cases, eradicate—infectious diseases requires public health and governmental leadership.

The public health system is responsible for total population health and must take the lead to finance, organize, monitor, and deliver needed services such as child vaccination. Public health widely suffers from low priority in national government budgets. Harmonization of immunization policies and public support are needed, as are resources. Strong support by national government policy and funding are key to the reduction in incidence, prevalence, and control of diseases which can be ameliorated by known, as well as yet-to-be discovered, vaccines.

Hilleman was undoubtedly the leading vaccinologist of the 20 th century, and perhaps of all time. It is recommended that these groups verify that they received two doses of mumps-containing vaccine, or demonstrate proof of mumps immunity. During recent outbreaks, mumps cases have occurred even in individuals who have received two doses of the vaccine, as a result of waning vaccine immunity.

In response, third doses have been given during outbreaks, with good booster responses to the vaccine. Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Atkinson, W. Vaccines: Mumps vaccination. Immunization Action Coalition. Mumps: Questions and answers. Plotkin, S.

Vaccines, 5th ed. Philadelphia: Saunders; World Health Organization. Mumps virus vaccines: WHO position paper. Weekly Epidemiological Record.

More information about the history of mumps and the development of mumps vaccines can be found in our Disease Timelines. Article Menu [ ]. Vaccine Science [ ]. Biological Weapons, Bioterrorism, and Vaccines. Cancer Vaccines and Immunotherapy. Careers in Vaccine Research. Ebola Virus Disease and Ebola Vaccines. Human Cell Strains in Vaccine Development. Identifying Pathogens and Transmission Vectors. Malaria and Malaria Vaccine Candidates.

Passive Immunization. The Future of Immunization. Vaccines for Pandemic Threats. Viruses and Evolution. History and Society [ ]. Cultural Perspectives on Vaccination. Symptoms usually resolve within 2 weeks, coincident with the development of a MuV-specific humoral response.

Long-term complications and death are rare. Approximately one-third to one-half of MuV infections are asymptomatic or result in only mild respiratory symptoms, sometimes accompanied by fever [ 45 — 49 ].

The hallmark of mumps is salivary gland swelling, typically the parotid glands, which forms the basis of a clinical diagnosis. Parotitis is usually bilateral, developing 2—3 weeks after exposure and lasting for 2—3 days, but it may persist for a week or more in some cases [ 37 , 50 , 51 ]. Submaxillary, submandibular and sublingual glands can be involved, but rarely as the only manifestation of mumps. Viral replication in the parotid gland results in perivascular and interstitial mononuclear cell infiltration, haemorrhage, oedema and necrosis of acinar and epithelial duct cells [ 52 ].

Serum and urine amylase levels may be elevated as a result of inflammation and tissue damage in the parotid gland [ 53 ]. Virus is excreted in the saliva from approximately 1 week before to 1 week after the onset of salivary gland swelling [ 37 , 54 , 55 ]. MuV has also been identified in the saliva of asymptomatic persons [ 37 ]. Coupled with excretion of virus up to 1 week before symptom appearance, this may explain some of the difficulties in controlling mumps outbreaks.

Orchitis, which is typically unilateral, is the most common extra-salivary gland manifestation of mumps. MuV has been recovered from semen and the testis, suggesting that epididymo-orchitis is the result of direct infection of testicular cells [ 58 , 59 ].

However, an indirect immune-mediated mechanism has also been postulated [ 60 ]. Both Leydig and germ cells are involved, associated with reduced levels of testosterone production [ 61 — 63 ]. Necrosis of acinar and epithelial duct cells is evident in the germinal epithelium of the seminiferous tubules of the testes.

Orchitis is almost always accompanied by epididymitis and fever, all resolving within 1 week. Atrophy of the involved testicle occurs in approximately half of cases and can be associated with oligospermia and hypofertility, but rarely sterility [ 58 , 62 , 64 , 65 ].

Oophoritis has been associated with infertility [ 67 ] and premature menopause [ 68 ], but such cases are extremely rare. Virus frequently disseminates to the kidneys, as suggested by the frequency of viruria during the established acute phase of the disease Figure 2 [ 69 , 70 ].

Epithelial cells of the distal tubules, calyces and ureters appear to be primary sites of virus replication [ 52 ]. Kidney involvement in mumps is almost always benign, but cases of severe interstitial nephritis have been reported. In such cases, renal biopsy or postmortem necropsy show evidence of immune complex deposition, interstitial mononuclear cell infiltration and fibrosis, oedema and focal tubular epithelial cell damage [ 71 — 73 ].

There are conflicting reports on the association between mumps pancreatitis and diabetes mellitus [ 75 — 79 ] and it is unclear whether there is a causal link. MuV is highly neurotropic, with evidence of central nervous system CNS involvement in up to half of all cases of infection, based on pleocytosis of the cerebrospinal fluid [ 48 , 80 — 82 ].

Symptomatic CNS infection is less common, but significant. Although these are small percentages, MuV was the leading cause of encephalitis in the USA until , when mumps-containing vaccine gained widespread use [ 83 ].

In unvaccinated populations, mumps continues to account for a high percentage of viral encephalitis cases [ 46 , 84 , 85 ]. Little is known of the CNS pathology, since the disease is rarely fatal. Of the few postmortem cases examined, the pathology includes oedema and congestion throughout the brain with haemorrhage, lymphocytic perivascular infiltration, perivascular glio-sis and demyelination, with relative sparing of neurons.

These latter observations suggest that in some cases of mumps encephalitis the inflammation stems from a para-infectious process. However, virus can be recovered from CSF early in the course of meningitis [ 86 , 87 ], as well as from brain tissue in some cases of mumps encephalitis. Experimental infection in rodents suggests the virus enters the CSF through the choroid plexus, or possibly via transiting mononuclear cells during viraemia. Based on animal data, once in the CSF, virus appears to be carried throughout the ventricular system, resulting in virus replication within ependymal cells that line the ventricles Figure 3A [ 44 ].

From these locations, virus can penetrate into the brain parenchyma, often infecting pyramidal cells in the cerebral cortex and hippocampus [ 88 ]. The infected ependymal epithelia become inflamed, lose their cilia, degenerate and collapse into the CSF Figure 3B , a postulated cause of the aqueductal stenosis that is believed to be responsible for the occurrence of hydrocephalus, typically of the lateral and third ventricles, a common outcome in intracerebrally injected animals [ 89 — 93 ].

Mumps hydrocephalus has been reported in humans, most often presenting as obstruction of the cerebral aqueduct with dilatation of the lateral and third ventricles. However, obstruction of the foramen of Monro between the lateral and third ventricles, or obstruction of the foramina of Magendie and Luschka between the fourth ventricle and the sub-arachnoid space, have also been reported [ 94 — 98 ].

The finding of ependymal cell debris in the CSF of mumps patients [ 94 , 96 , 99 ] suggests that the pathogenesis of hydrocephalus in experimentally infected animals is similar to the mechanism of hydrocephalus in humans. However, hydrocephalus has been observed before, or in the total absence of, canal obstruction [ 88 , 91 , , ], indicating that such events could be a secondary consequence of external compression by surrounding oedematous tissue and not causally related to the pathogenesis of hydrocephalus.

MuV infection of the rat brain. The most prominent neuropathological outcome following MuV intracranial inoculation in small animal models hamsters, rats is enlargement of the lateral and third ventricles, ie hydrocephalus, which has also been reported in cases in humans. The cause of hydrocephalus is postulated to be denuding of virus-infected ependymal cells lining the ventricles. A Sagittal section of rat brain tissue immunohistochemically stained for the MuV nucleoprotein, showing extensive infection of the ventricular ependymal cells green foci.

Hearing loss is typically unilateral and transient, but can be permanent [ — ]. Pathological findings include lesions and degeneration of the stria vascularis, tectorial membrane and organ of Corti [ , ]. MuV infection of the CSF has been implicated in the pathogenesis of deafness in mumps, given the detection of the virus in perilymph, which freely communicates with the CSF [ ].

This is also supported by animal studies, where instillation of the virus into the CSF has resulted in infection of the cochlea [ ]. However, deafness does not occur any more frequently in patients with meningitis or encephalitis than it does in patients lacking signs of CNS infection, suggesting that CSF may in fact not be involved in the pathogenesis of deafness.

An alternative explanation could be that virus infects the inner ear via a haematogenous route, ie that mumps labyrinthitis occurs as a consequence of viraemia. Hearing loss caused by indirect effects of virus infection eg immune-mediated damage have also been suggested [ ].

MuV was also identified in the vestibular ganglia in experimentally infected animals [ ], which likely also occurs in humans and explains vestibular symptoms, such as vertigo, which often present in cases of mumps deafness [ , ]. Based on electrocardiographic abnormalities in mumps patients, MuV likely infects cardiac tissue [ ]. While this is rarely symptomatic, interstitial lymphocytic myocarditis and pericarditis have been reported [ ], which can lead to endocardial fibroelastosis [ ].

MuV has also been identified in cardiac muscle from patients with these disorders. Clinically apparent cardiac complications are rare, but can be serious [ , , ].

Other rare complications include cerebellar ataxia [ , ], transverse myelitis [ , ], ascending polyradiculitis [ ], a poliomyelitis-like disease [ , ], arthropathy [ , ], autoimmune haemolytic anaemia [ , ], thyroiditis [ , ], thrombocytopenia [ , ], hepatitis [ , ] and retinitis and corneal endotheliitis [ — ]. Transplacental transmission of the virus has been demonstrated in non-human primates [ ] and is suggested by the isolation of virus from the human fetus following spontaneous or planned abortion during maternal mumps [ — ].

Aborted fetal tissue from such cases has been found to exhibit a proliferative necrotizing villitis with decidual cells containing intracytoplasmic inclusions [ ].

Virus has also been isolated at birth from infants born to women with mumps [ ] and from breast milk [ ], but few cases of perinatal mumps have been described [ , ] and it is not clear whether breast milk was responsible for these cases.

Mumps virus does not appear to cause congenital malformations [ ]. The major morbidity from mumps is from complications of meningitis, encephalitis and orchitis. The case fatality ratio is 1. Historically, the most widely used animal models of mumps have been the hamster and the monkey, and information from these models serves as the basis for much of our current understanding of MuV pathogenesis and disease. However, the relevance of findings in these models for humans is questionable, given the use of unnatural routes of inoculation eg intracranial, intraperitoneal or intravenous and the inability of these models to clearly and reliably discriminate strains that are attenuated for humans from wild-type, virulent strains [ — ].

In the one study where monkeys rhesus macaques were inoculated via natural routes intranasal and intratracheal , only wild-type virus was tested [ ]. Nonetheless, this study demonstrated the potential to identify sites of early and late MuV replication, which supports further evaluation of this model. Mice and ferrets were also explored as model systems; however, virus replication in these species is self-limiting, making them poor candidates for pathogenesis studies [ — ]. A key advance in the study of MuV pathogenesis was the development of a rat model predictive of the neurovirulence potential of MuV strains for humans.

In this model, 1 month after intracerebral injection of virus into newborn Lewis rats, brains are removed and evaluated for virus-induced hydrocephalus Figure 4 , the severity of which correlates with the neurovirulence potential of the virus for humans [ ]. With the advent of plasmid-based reverse genetics systems for MuV, it became possible to examine molecular determinants of virulence, and thus gain a better understanding of virus factors that influence pathogenicity. The first such study was published by Lemon et al [ ], who generated Jeryl Lynn vaccine strain-based viruses expressing genes derived from the Kilham MuV strain, a hamster brain-adapted laboratory strain.

Of the single gene replacements assessed M , F , SH and HN , only the F gene was found to significantly increase the neurovirulence potential of the highly attenuated Jeryl Lynn strain [ ]. However, in a subsequent study using a different virulent MuV strain, , Sauder et al [ ] found the F gene to have no biologically meaningful effect on the neurovirulence potential of Jeryl Lynn.

MuV strain-specific molecular determinants of virulence are also highlighted in other studies. For example, Xu et al [ ] identified the SH gene as a virulence factor for the wild-type IA MuV strain, whereas Malik et al [ 32 ] found no such role for the SH gene in virulence. Of additional interest, in the Sauder et al study, the Jeryl Lynn genes found to neuro-attenuate the strain eg M , HN and L , when derived from the strain, did not meaningfully increase the neurovirulence of the Jeryl Lynn virus.

Thus, not only do genes that influence virulence of one strain often not affect virulence of another strain, but genes involved in neurovirulence are not necessarily involved in neuroattenuation. Taken together, these results raise doubt as to the prospect of identifying broadly applicable genetic determinants of virulence and attenuation.

An alternative, or complementary, approach may be to examine differences between virulent and attenuated strains in terms of sites of primary replication and spread, following infection via natural routes in disease-relevant animal models. To this end, new in vitro and in vivo model systems that recapitulate the diverse features of a natural infection are needed. Hydrocephalus severity in MuV-infected rats. B T1 weighted gradient-echo image from MRI of the same brains as in A upper left corner and lower right corner , compared to brain from a rat injected with an insufficiently attenuated vaccine strain, Urabe-AM9 Ur, lower left corner and an uninfected rat brain 0, upper right corner.

As a re-emerging pathogen, with concerns over vaccine safety and efficacy, elucidation of mechanisms of MuV pathogenesis is of paramount importance, as this information will help direct the development of improved vaccines.

The utilization of existing reverse genetic systems alongside the generation of new, clinically relevant systems and the development of robust animal models for other aspects of the disease will allow a more complete understanding of disease. This review has summarized our current understanding of MuV clinical disease, pathology, and how this relates to viral pathogenesis.

However, a number of areas are evidently poorly understood and important questions remain Figure 5. These include the elucidation of the target cell tropism throughout an infection, the mechanisms by which MuV establishes a systemic infection and the basis of neurotropism. Determination of these likely requires the establishment of a primate model of MuV infection, similar to what has been achieved with measles.

The measles system, exploiting a fluorescent reporter-expressing wild-type MV in a clinically-relevant macaque Macaca fascicularis model has facilitated the elucidation of key features of measles virus pathogenesis relevant to disease, transmission and immunity [ 40 ]. Applying what has been learned from the measles model to mumps will provide an ideal basis to understanding determinants of MuV pathogenesis.

A number of important questions remain unresolved regarding MuV pathogenesis. This is of particular relevance to renewed efforts towards development of a more efficacious MuV vaccine, in light of the resurgence of mumps in vaccinated populations.

The classic method of virus attenuation is extensive blind passage in vitro. While this often leads to the desired effect of a loss of virulence and reactogenicity, it can also lead to loss of immunogenicity and efficacy. Clearly, a more rational approach to virus attenuation is needed, and understanding the natural pathogenesis of the infectious agent is a prerequisite to any such endeavour.

This figure highlights this issue, showing our current assumptions of pathogenesis black text and unresolved questions red text. No conflicts of interest were declared. National Center for Biotechnology Information , U. J Pathol. Author manuscript; available in PMC Jan 1.

Author information Copyright and License information Disclaimer. Copyright notice. The publisher's final edited version of this article is available at J Pathol. See other articles in PMC that cite the published article. Abstract Mumps is caused by the mumps virus MuV , a member of the Paramyxoviridae family of enveloped, non-segmented, negative-sense RNA viruses.

Keywords: mumps, mumps virus, pathogenesis, neurovirulence, vaccine. Open in a separate window. Figure 1. Clinical features, pathogenesis and pathology Given the incidence of mumps in the pre-vaccine era, comparatively little is known about the pathogenesis of the disease. Initial infection: targeting of the upper respiratory tract epithelium?

Systemic spread: from epitheliotropic to lymphotropic? Figure 2. CNS involvement: from lymphotropic to neurotropic MuV is highly neurotropic, with evidence of central nervous system CNS involvement in up to half of all cases of infection, based on pleocytosis of the cerebrospinal fluid [ 48 , 80 — 82 ].

Figure 3. Animal models and molecular determinants of MuV pathogenesis Historically, the most widely used animal models of mumps have been the hamster and the monkey, and information from these models serves as the basis for much of our current understanding of MuV pathogenesis and disease. Figure 4. In that year, two French physicians, Charles-Jean-Henri Nicolle and Ernest Alfred Conseil, attempted to transmit mumps from humans to monkeys, but were unable to obtain conclusive results.

Eight years later, Martha Wollstein injected viruses taken from the saliva of a mumps patient into cats, producing inflammation of the parotid, testes, and brain tissue in the cats. Conclusive proof that mumps is transmitted by a filterable virus was finally obtained by two American researchers, Claude D. Johnson and Ernest William Goodpasture , in A vaccine for mumps was developed by an American microbiologist, John Enders, in During World War II, Enders had developed a vaccine using a killed virus, but it was only moderately and temporarily successful.

After the war, he began to investigate ways of growing mumps virus in a suspension of minced chick embryo and ox blood. The technique was successful and Enders' live virus vaccine is now routinely used to vaccinate children against this ancient disease.