After high vaccination coverage, mumps incidence dropped by half in from its peak in Notably, mumps incidences slightly increased from to This may be due to the fact that more than 10 years have passed since the first one dose vaccine was administered, and vaccine effectiveness has declined.
Figure 2 Annual mumps cases reported in China from to Data come from reports of the National Health Commission of China. The recent resurgence of mumps mainly involved adolescents and young adults, with high rates of orchitis frequently reported 3 , 33 — Unvaccinated postpubertal males are susceptible to virus outbreaks and are at high risk of developing mumps orchitis.
In China, the vaccination rate of men born in the s, who are now 30 years old, is low due to lacking MMR vaccination program in less developed areas. Thus, it is essential to be aware of this epidemiological shift and the resurgence of mumps orchitis in the clinic. Cases of orchitis following MMR vaccination are reported in post-pubertal adults, suggesting that the MMR vaccination may have an adverse effect on the testis in certain young adults 38 — Therefore, whether unvaccinated male in this age group should be offered the MMR vaccine requires in-depth and carefully evaluation.
Mumps orchitis usually occurs at about one week after the onset of parotitis in young adult males with MuV infection. The onset of orchitis is associated with constitutional symptoms, such as headache and fever and later manifests as testicular swollen and pain.
Examination of the scrotum generally indicates swelling testes, associated tenderness, and inflammation of the scrotum. Epididymitis also occurs in most of the mumps orchitis cases and results in mumps epididymo-orchitis 42 , A recent study demonstrates that the epididymal head is mostly involved in mumps epididymo-orchitis, which is in contrast to bacterial epididymitis that commonly occurs in the cauda epididymis 44 , During the acute phase, the endocrine function of the testes is altered, e.
Some cases also show increased luteinizing hormone LH and follicle-stimulating hormone FSH levels The acute symptoms can resolve within two weeks; however, testicular atrophy can occur in half of the orchitis patients and is characterized by an oblong shape, low echogenicity, and decreased vascularity based on ultrasonographic findings 3 , However, seminal abnormalities, including sperm count, motility and morphology, may sustain for years after recovery 37 , suggesting the abnormal spermatogenesis can occur.
There is no standard criteria procedure for MuV diagnosis because it is not a common condition that is observed in hospital.
Diagnosis of MuV is mainly based on clinical complication and laboratory testing. Orchitis characteristically presents with swollen and pain testes. Ultrasonography can provide image features, including low echogenicity, hypervascularity, and increased volume of the testes and epididymis 43 , Testicular inflammation and hydrocele could also be detected. The routine urine analysis is necessary for diagnosing the mumps orchitis to rule out bacterial infection The definitive diagnosis of mumps orchitis should be based on laboratory tests.
While MuV can be isolated from the seminal fluid within two weeks after symptom onset 50 , the test for viral infectivity is usually not performed in the clinical diagnosis due to the complicated procedure for this test. MuV infection is mostly self-limiting, and there is currently no specific antiviral therapy available.
The treatment for mumps orchitis generally includes supportive procedures, including bed rest, scrotal support, and analgesic and anti-inflammatory drugs against pain and fever. Steroid drugs were used to diminish testicular pain and swelling, but it does not alter the clinical course and prevent subsequent atrophy.
Interferon has been used in a series of cases to cure mumps orchitis; however, this is a controversial method because there is conflicting evidence on its therapeutic effect. Erpenbach et al. However, Yeniyol et al. It is difficult to study the pathogenesis of mumps orchitis in humans due to the lack of samples.
Recent studies using mouse models provide insights to mechanisms by which MuV infects testicular cells and impairs testicular functions Figure 3. Figure 3 Schematic of MuV infection of testicular somatic cells and downstream effects. MuV infection of LC inhibits testosterone synthesis. SOCS, suppressor of cytokine signaling. The red dashed line indicates a possible signaling pathway in SCs and LCs according to previous findings 54 — It is well-known that MuV has high tropism to the testis Thus, understanding the mechanism of receptor recognition by MuV is very important.
Sialic acid, which is expressed on the cell surface as a terminal component of sugar chains, plays a role in mediating infection of many viruses, including influenza viruses 58 , the Middle East respiratory syndrome coronavirus 59 , and Zika virus ZIKV The MuV-HN-receptor interaction triggers the activation of the F protein, causing fusion of the viral envelope with the plasma membrane and allowing cell entry A very recent study has confirmed the presence of sialic acid on the surface of Sertoli cells SCs and Leydig cells LCs These results suggest that other co-receptors for MuV binding to testicular cells exist.
Whether these receptors function for MuV tropism toward testicular cells requires further investigation. Other types of cell receptors such as AXL and MER, which are members of a subfamily of receptor tyrosine kinases, have been suggested as potential candidates for MuV tropism. AXL and MER have been suggested to function as binding or entry factors for MuV based on the observation that these are highly expressed in the testis during MuV infection 63 , However, a genetic study showed that double knockout of both Axl and Mer remarkably decreased MuV replication, whereas single knockout of either Axl or Mer barely affected MuV replication.
These findings on the mechanism underlying receptors-mediated MuV binding, internalization and replication Figure 3 may be helpful discovering the targets for the prevention of MuV infection.
Due to the lack of testicular biopsy from mumps orchitis patients, it is difficult to investigate MuV infection and pathogenesis in the testis. Although humans are believed to be the only natural reservoir, MuV was experimentally used to infect various animal models to evaluate protective immunity against MuV 8 , Unfortunately, studies on the pathogenesis of orchitis in the animal models are limited.
However, MuV differentially replicates in these testicular cells. In contrast, MuV does not replicate in male GCs. These findings suggest that testicular cells exhibit different innate antiviral responses against MuV replication.
To understand the mechanisms underlying MuV-induced orchitis, a recent study investigated the pattern recognition receptors-initiated innate immune responses of testicular cells to MuV infection These investigations suggest that TLR2 plays a crucial role in initiating the innate immune responses to MuV infection in testicular cells.
Usually, viral replication in infected cells is restricted by cellular innate antiviral responses. Remarkably, GCs and TMs are equipped with autophagy machineries, and autophagy restricts MuV replication in these cells.
These findings suggest a cell type-specific innate antiviral mechanisms against MuV replication in testicular cells.
Notably, viral infection in male GCs may be sexually transmitted to female partners and fetus, thus leading to virus parallel and vertical transmission The antiviral defense of male GCs is particularly important not only for male fertility but also for limiting virus transmission.
The innate antiviral responses in most type of cells after viral infection produce type 1 IFNs and various pro-inflammatory cytokines The increased levels of certain pro-inflammatory cytokines can be harmful to spermatogenesis However, autophagy directly uptakes and degrades viruses that invade GCs, without the induction of pro-inflammatory cytokines Therefore, autophagy of male GCs should be suitable for the antiviral defense without harming spermatogenesis.
The cytokines induced by viral infection can mediate organ dysfunction and tissue damage We recently found that MuV infection induced the production of various pro-inflammatory cytokines and inhibited testosterone synthesis in LCs The BTB plays an important role in maintaining normal spermatogenesis.
Moreover, a recent study showed that the exposure of SCs to inflammatory mediators derived from ZIKV-infected macrophages also led to the degradation of the ZO-1 protein, which correlated with increased BTB permeability During spermatogenesis, a large number of novel antigens are produced by post-meiotic spermatids in seminiferous tubules after immune self-tolerance has been established The production of autoantibodies against GC antigens is a common feature for orchitis patients.
This may explain why mumps orchitis often causes male infertility in postpubertal and young adult men but rarely affects children when the spermatids have not yet been produced in the testes. The deleterious effects of MuV infection on male GCs have also been examined in a recent study CXCL10 is a pleiotropic cytokine capable of exerting various functions, including the chemotaxis of leucocytes and induction of apoptosis Laboratory animal models are critical for the studies on the pathogenesis of MuV-induced diseases.
Unfortunately, mice are not susceptible to MuV infection. Although MuV efficiently replicates in mouse testicular cells in vitro , this is not evident in vivo The detrimental effects of ZIKV on the testis are only occurred in mice lacking interferon signaling but not in WT mice A recent study showed that mice lacking type 1 interferon signaling were susceptible to MuV infection Alternatively, a mouse cell-adapted MuV strain may be used to establish an orchitis model, but how far the observations in mouse models are relevant to human remains questionable.
The recent outbreaks occurring in highly vaccinated populations have sparked renewed interest in mumps and complications, particularly orchitis. There is a growing concern that a group of mumps cases has shifted from children to young adults and is associated with a high rate of orchitis and severe reproductive problems.
The mechanisms behind the development of mumps and orchitis are unknown. Several recent studies on MuV based on primary cells have improved our understanding of mumps virus pathogenesis with regard to MuV receptors-testicular cells interaction, innate immune responses to MuV infection, and detrimental effects on testicular function using mouse models.
However, a number of knowledge gaps remain. MuV can effectively replicate in mouse testicular cells in vitro. The testis is an immunoprivileged organ for the protection of the spermatozoon from adverse immune response Whether the testicular immune privilege status provides a refuge for MuV replication to escape immune surveillance requires clarification.
Rare orchitis cases after the MMR vaccination were reported, suggesting a potential risk of the vaccination 38 — 41 , The pathogenesis of the vaccination-related orchitis remains uncertain and is worth investigating further.
In-depth understanding of these questions would help in the development of preventative and therapeutic approaches for mumps orchitis and male infertility. DH and HW designed the concept and wrote the manuscript. DT and FW collected materials and prepared figures.
All authors contributed to the article and approved the submitted version. The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. Lancet — As well as swollen testicles, these can include inflammation of the ovaries, aseptic meningitis, acute inflammation of the brain, deafness and pancreatitis. They also need to ensure that male patients in this high-risk group are vaccinated and educated about the risks and complications of the virus.
Materials provided by Wiley - Blackwell. Note: Content may be edited for style and length. Science News. Story Source: Materials provided by Wiley - Blackwell. Journal Reference : Davis et al. The increasing incidence of mumps orchitis: a comprehensive review. ScienceDaily, 31 March A study of a recent mumps outbreak on a college campus showed that students who received a third dose of MMR vaccine had a much lower risk of contracting the disease.
The MMR vaccine is very safe and effective. Getting the MMR vaccine is much safer than getting mumps. Most people experience no side effects from the vaccine. Some people experience a mild fever or rash or achy joints for a short time. Rarely, children who get the MMR vaccine might experience a seizure caused by fever. But these seizures haven't been associated with any long-term problems. Mayo Clinic does not endorse companies or products.
Advertising revenue supports our not-for-profit mission. This content does not have an English version. This content does not have an Arabic version. Overview Salivary glands Open pop-up dialog box Close. Salivary glands You have three pairs of major salivary glands — parotid, sublingual and submandibular. Mumps Open pop-up dialog box Close. Mumps Mumps is characterized by swollen, painful salivary glands in the face, causing the cheeks to puff out.
Request an Appointment at Mayo Clinic. Share on: Facebook Twitter. Show references Kliegman RM, et al. In: Nelson Textbook of Pediatrics. Philadelphia, Pa. Accessed July 14, Centers for Disease Control and Prevention.
0コメント