Modeling the population-level impact of a third dose of MMR vaccine on a mumps outbreak at the University of Iowa.

Mumps outbreaks among fully vaccinated young adults have raised questions about potential waning of immunity over time and need for a third dose of the measles, mumps, rubella (MMR) vaccine. However, there are currently limited data on real-life effectiveness of the third-dose MMR vaccine in preventing mumps. Here, we used a deterministic compartmental model to infer the effectiveness of the third-dose MMR vaccine in preventing mumps cases by analyzing the mumps outbreak that occurred at the University of Iowa between August 24, 2015, and May 13, 2016. The modeling approach further allowed us to evaluate the population-level impact of vaccination by different timing in relation to the start of the outbreak and varied coverage levels, and to account for potential sources of bias in estimating vaccine effectiveness. We found large uncertainty in vaccine effectiveness estimates; however, our models showed that early introduction of a third dose of MMR vaccine during a mumps outbreak can be effective in preventing transmission. School holidays, such as the winter break, likely played important roles in preventing mumps transmission.

Disentangling the causes of mumps reemergence in the United States.

Over the past two decades, multiple countries with high vaccine coverage have experienced resurgent outbreaks of mumps. Worryingly, in these countries, a high proportion of cases have been among those who have completed the recommended vaccination schedule, raising alarm about the effectiveness of existing vaccines. Two putative mechanisms of vaccine failure have been proposed as driving observed trends: 1) gradual waning of vaccine-derived immunity (necessitating additional booster doses) and 2) the introduction of novel viral genotypes capable of evading vaccinal immunity. Focusing on the United States, we conduct statistical likelihood-based hypothesis testing using a mechanistic transmission model on age-structured epidemiological, demographic, and vaccine uptake time series data. We find that the data are most consistent with the waning hypothesis and estimate that 32.8% (32%, 33.5%) of individuals lose vaccine-derived immunity by age 18 y. Furthermore, we show using our transmission model how waning vaccine immunity reproduces qualitative and quantitatively consistent features of epidemiological data, namely 1) the shift in mumps incidence toward older individuals, 2) the recent recurrence of mumps outbreaks, and 3) the high proportion of mumps cases among previously vaccinated individuals.

A highly efficacious live attenuated mumps virus-based SARS-CoV-2 vaccine candidate expressing a six-proline stabilized prefusion spike.

With the rapid increase in SARS-CoV-2 cases in children, a safe and effective vaccine for this population is urgently needed. The MMR (measles/mumps/rubella) vaccine has been one of the safest and most effective human vaccines used in infants and children since the 1960s. Here, we developed live attenuated recombinant mumps virus (rMuV)-based SARS-CoV-2 vaccine candidates using the MuV Jeryl Lynn (JL2) vaccine strain backbone. The soluble prefusion SARS-CoV-2 spike protein (preS) gene, stablized by two prolines (preS-2P) or six prolines (preS-6P), was inserted into the MuV genome at the P-M or F-SH gene junctions in the MuV genome. preS-6P was more efficiently expressed than preS-2P, and preS-6P expression from the P-M gene junction was more efficient than from the F-SH gene junction. In mice, the rMuV-preS-6P vaccine was more immunogenic than the rMuV-preS-2P vaccine, eliciting stronger neutralizing antibodies and mucosal immunity. Sera raised in response to the rMuV-preS-6P vaccine neutralized SARS-CoV-2 variants of concern, including the Delta variant equivalently. Intranasal and/or subcutaneous immunization of IFNAR1-/- mice and golden Syrian hamsters with the rMuV-preS-6P vaccine induced high levels of neutralizing antibodies, mucosal immunoglobulin A antibody, and T cell immune responses, and were completely protected from challenge by both SARS-CoV-2 USA-WA1/2020 and Delta variants. Therefore, rMuV-preS-6P is a highly promising COVID-19 vaccine candidate, warranting further development as a tetravalent MMR vaccine, which may include protection against SARS-CoV-2.

Novel sialidase inhibitors suppress mumps virus replication and infection.

The prevalent human pathogen, mumps virus (MuV; orthorubulavirus parotitidis) causes various complications and serious sequelae, such as meningitis, encephalitis, deafness, and impaired fertility. Direct-acting antivirals (DAAs) targeting MuV which can prevent mumps and mumps-associated complications and sequelae are yet to be developed. Paramyxoviridae family members, such as MuV, possess viral surface hemagglutinin-neuraminidase (HN) protein with sialidase activity which facilitates efficient viral replication. Therefore, to develop DAAs targeting MuV we synthesized MuV sialidase inhibitors. It is proposed that the viral HN has a single functional site for N-acetylneuraminic acid (Neu5Ac) binding and sialidase activity. Further, the known MuV sialidase inhibitor is an analog of Neu5Ac-2,3-didehydro-2-deoxy-N-acetylneuraminic acid (DANA)-which lacks potency. DANA derivatives with higher MuV sialidase inhibitory potency are lacking. The MuV-HN-Neu5Ac binding site has a hydrophobic cavity adjacent to the C4 position of Neu5Ac. Exploiting this, here, we synthesized DANA derivatives with increasing hydrophobicity at its C4 position and created 3 novel sialidase inhibitors (Compounds 1, 2, and 3) with higher specificity for MuV-HN than DANA; they inhibited MuV replication step to greater extent than DANA. Furthermore, they also inhibited hemagglutination and the MuV infection step. The insight-that these 3 novel DANA derivatives possess linear hydrocarbon groups at the C4-hydroxyl group of DANA-could help develop highly potent sialidase inhibitors with high specificity for MuV sialidase, which may function as direct-acting MuV-specific antivirals.

Long-term persistence of seroprotection against measles following measles-mumps-rubella vaccination administered before and after pediatric liver transplantation.

Liver transplantation (LT) recipients are susceptible to infections, including measles. Concerns about the safety and efficacy of live-attenuated vaccines, such as the measles-mumps-rubella (MMR) vaccine, have led to hesitancy among providers in administering them to immunocompromised patients. This 9-year interventional study assessed seroprotection against measles following MMR vaccination in pediatric LT recipients. Of 119 participants enrolled, 60 (50%) were seroprotected against measles after transplantation. Among the 59 nonseroprotected participants, 56 fulfilled safety criteria and received MMR vaccination with a seroprotection rate of 90% (95% confidence interval [CI], 73%-98%) after a first dose, 95% (95% CI, 85%-99%) after primary vaccination with 1 to 3 doses, comparable to nonimmunocompromized populations. However, measles antibodies declined over time, suggesting the need for regular monitoring, and booster doses. Half of the vaccinees (26/53, 49%) subsequently lost seroprotection. Among them, 23 received additional doses of MMR, with a high seroconversion rate. At their last follow-up (median, 6.1 years; interquartile range, 3.0-8.1 after inclusion), 63% (95% CI, 49%-75%) of all vaccinees were seroprotected against measles. In conclusion, MMR vaccination in pediatric LT recipients offers seroprotection against measles, but long-term immunity should be monitored closely.

Assessing clinical benefits of live-attenuated vaccination in post-liver transplant patients: Analysis of breakthrough infections and natural boosters.

Recently, live-attenuated measles, rubella, varicella, and mumps vaccines have been administered to carefully selected post-liver transplant patients. Although attention has been focused on post-vaccination antibody titers and adverse events, the real-life clinical benefits remain unclear. A comprehensive analysis of breakthrough infections and natural boosters (asymptomatic cases with significant elevation in virus antibody titers) following immunization post-liver transplantation was conducted from 2002-2023, exploring the timing, frequency, correlation with domestic outbreaks, and degree of antibody elevation. During the median 10-year observation period among 68 post-liver transplant patients, breakthrough infections occurred only in chickenpox, with 7 mild cases (1 episode/64 person-years). A total of 59 natural booster episodes (1, 5, 20, and 33 for measles, rubella, chickenpox, and mumps, respectively) were observed, with incidence rates of 1 per 569, 110, 22, and 17 person-years, respectively. The timing of natural boosters closely correlated with domestic outbreaks (P < .05 in chickenpox and mumps), influenced by local vaccine coverage. The degree of antibody elevation was significantly higher in individuals with breakthrough infections than in those with natural boosters (P < .05). These findings suggest that immunization with live-attenuated vaccines for post-liver transplant patients has demonstrated clinical benefits. Furthermore, mass vaccination has a positive impact on post-transplant patient outcomes.

Evaluation of the Interactions between Mumps Virus and Guinea Pig.

Mumps is a highly contagious viral disease that can be prevented by vaccination. In the last decade, we have encountered repeated outbreaks of mumps in highly vaccinated populations, which call into question the effectiveness of available vaccines. Animal models are crucial for understanding virus-host interactions, and viruses such as mumps virus (MuV), whose only natural host is the human, pose a particular challenge. In our study, we examined the interaction between MuV and the guinea pig. Our results present the first evidence that guinea pigs of the Hartley strain can be infected in vivo after intranasal and intratesticular inoculation. We observed a significant viral replication in infected tissues up to 5 days following infection and induction of cellular and humoral immune responses as well as histopathological changes in infected lungs and testicles, without clinical signs of disease. Transmission of the infection through direct contact between animals was not possible. Our results demonstrate that guinea pigs and guinea pig primary cell cultures represent a promising model for immunological and pathogenetic studies of the complex MuV infection. IMPORTANCE Understanding of mumps virus (MuV) pathogenesis and the immune responses against MuV infection is limited. One of the reasons is the lack of relevant animal models. This study explores the interaction between MuV and the guinea pig. We demonstrated that all tested guinea pig tissue homogenates and primary cell cultures are highly susceptible to MuV infection and that α2,3-sialylated glycans (MuV cellular receptors) are being abundantly expressed at their surface. The virus remains in the guinea pig lungs and trachea for up to 4 days following intranasal infection. Although asymptomatic, MuV infection strongly activates both humoral and cellular immune response in infected animals and provides protection against virus challenge. Infection of the lungs and testicles after intranasal and intratesticular inoculation, respectively, is also supported by histopathological changes in these organs. Our findings give perspective for application of guinea pigs in research on MuV pathogenesis, antiviral response, and vaccine development and testing.

Epidemiological characteristics and serological survey of mumps 15 years after MMR vaccine was included in the immunization program.

Mumps is a vaccine-preventable acute viral infectious disease. To understand the incidence of mumps and population immunity in Quzhou City after measles mumps rubella vaccine (MMR) was included in the immunization program, we analyzed the epidemiological characteristics of mumps cases from 2009 to 2023 and a cross-sectional serosurvey of IgG antibodies to mumps conducted in 2024. We found that 15 years after the MMR vaccine was included in the immunization program, the incidence of mumps was significantly reduced in all populations, but the incidence remained highest in vaccinated children aged 0-12 years. Vaccine escape may explain the high incidence of mumps in highly vaccinated populations. Updating vaccines or developing a new vaccine that targets multiple viral genotypes may be necessary to improve the effectiveness of the vaccine against infection and fully control infections and outbreaks. The positive rate and concentration of mumps IgG antibody were inconsistent with the incidence data. mumps IgG antibody is not an ideal substitute for immunity and cannot be used to accurately predict whether a target population is susceptible or protected. Natural infections may provide longer-lasting immunity than vaccination.

Cytotoxic and viricidal effects of human semen on mumps virus-infected lymphocytes: In vitro studies.

Viruses in human semen may be sexually transmitted via free and cell-mediated viral infection. The potential effects of semen on the infection and sexual transmission of most viruses in semen remain largely unclear. The present study elucidated the inhibitory effects of human seminal plasma (SP) on Jurkat cell (JC)-mediated mumps virus (MuV) infection. We demonstrated that MuV efficiently infected JCs and that the JCs infected by MuV (JC-MuV) mediated MuV infection of HeLa cells. Remarkably, SP was highly cytotoxic to JCs and inhibited JC-MuV infection of HeLa cells. The cytotoxic factor possessed a molecular weight of less than 3 kDa, whereas that of the viricidal factor was over 100 kDa. The cooperation of cytotoxic and viricidal factors was required for the SP inhibition of JC-MuV infection, and prostatic fluid (PF) was responsible for both the cytotoxic and viricidal effects of SP. The cytotoxic effects we observed were resistant to the treatment of PF with boiling water, proteinase K, RNase A, and DNase I. Our results provide novel insights into the antiviral properties of SP, which may limit cell-mediated sexual viral transmission.

Long-Lived Plasma Cells Are Contained within the CD19(-)CD38(hi)CD138(+) Subset in Human Bone Marrow.

Antibody responses to viral infections are sustained for decades by long-lived plasma cells (LLPCs). However, LLPCs have yet to be characterized in humans. Here we used CD19, CD38, and CD138 to identify four PC subsets in human bone marrow (BM). We found that the CD19(-)CD38(hi)CD138(+) subset was morphologically distinct, differentially expressed PC-associated genes, and exclusively contained PCs specific for viral antigens to which the subjects had not been exposed for more than 40 years. Protein sequences of measles- and mumps-specific circulating antibodies were encoded for by CD19(-)CD38(hi)CD138(+) PCs in the BM. Finally, we found that CD19(-)CD38(hi)CD138(+) PCs had a distinct RNA transcriptome signature and human immunoglobulin heavy chain (VH) repertoire that was relatively uncoupled from other BM PC subsets and probably represents the B cell response's "historical record" of antigenic exposure. Thus, our studies define human LLPCs and provide a mechanism for the life-long maintenance of anti-viral antibodies in the serum.

Genetic characteristic of mumps virus from 2012 to 2016 and its serum antibody level among general healthy population during 2018-2020 in Jiangsu Province, China.

Mumps is a vaccine-preventable disease with high contagious capability. Its incidence declined rapidly since one dose of mumps vaccine was introduced into Expanded Program of Immunization (EPI) in 2008 in China. Nonetheless, the outbreaks of mumps remain frequent in China. Here we aim to assess herd immunity level followed by one-dose mumps ingredient vaccine and to elucidate the genetic characteristics of mumps viruses circulating in the post vaccine era in Jiangsu province of China. The complete sequences of mumps virus small hydrophobic(SH) gene were amplified and sequenced; coalescent-based Bayesian method was used to perform phylogenetic analysis with BEAST 1.84 software. Commercially available indirect enzyme-linked immune-sorbent IgG assay was used for the quantitative detection of IgG antibody against mumps virus. Our results show that genotype F was the predominant mumps viruses and belonged to indigenous spread, and most of Jiangsu sequences clustered together and formed a monophyly. The prevalence of mumps reached a peak in 2012 and subsequently declined, which presented an obvious different trajectory with virus circulating in other regions of China. The gene diversity of viruses circulating in Jiangsu province was far less than those in China. The antibody prevalence reached 70.42% in the general population during 2018 to 2020. The rising trend of antibody level was also observed. Although mumps antibody prevalence does not reach expected level, mumps virus faces higher pressure in Jiangsu province than the whole of China. To reduce further the prevalence of mumps viruses, two doses of mumps vaccine should be involved into EPI.

Assessing seropositivity of MMR antibodies in individuals aged 2-22: evaluating routine vaccination effectiveness after the 2003 mass campaign-a study from Iran's National Measles Laboratory.

BACKGROUND AND PURPOSE: The seroprevalence of antibodies against measles, mumps, and rubella (MMR) was evaluated 17 years following a mass vaccination campaign in individuals aged 2 to 22 years who had received routine immunization but were not eligible for an extended immunization program. METHODS: Samples were acquired from Iran's National Measles Laboratory (NML), with individuals showing positive IgM results excluded. Out of the samples collected in 2020, a random selection of 290 serum samples was chosen, representing individuals between the ages of 2 and 22 years from diverse regions in the country. These samples were subjected to analysis using an enzyme-linked immunosorbent assay (ELISA) to quantify specific IgG antibodies against MMR. RESULTS: The seroprevalence rates of antibodies for measles, mumps, and rubella were determined to be 76.2%, 89.3%, and 76.9%, respectively. Younger age groups exhibited higher seropositivity rates for measles and mumps, whereas the 7- to 11-year-old group demonstrated the highest seropositivity rate for rubella. A reduction in antibody status was observed from younger to older age groups, particularly those aged 17-22. CONCLUSION: The study unveiled suboptimal antibody levels for measles and rubella, highlighting the necessity for further investigation and potential adjustments to future vaccination strategies. Moreover, the decline in antibody status post-vaccination can accumulate in seronegative individuals over time, elevating the risk of outbreaks.

Live-attenuated vaccination for measles, mumps, and rubella in pediatric liver transplantation.

BACKGROUND: Infections are a serious short- and long-term problem after pediatric organ transplantation. In immunocompromised patients, they can lead to transplant rejection or a severe course with a sometimes fatal outcome. Vaccination is an appropriate means of reducing morbidity and mortality caused by vaccine-preventable diseases. Unfortunately, due to the disease or its course, it is not always possible to establish adequate vaccine protection against live-attenuated viral vaccines (LAVVs) prior to transplantation. LAVVs such as measles, mumps, and rubella (MMR) are still contraindicated in solid organ transplant recipients receiving immunosuppressive therapy (IST), thus creating a dilemma. AIM: This review discusses whether, when, and how live-attenuated MMR vaccines can be administered effectively and safely to pediatric liver transplant recipients based on the available data. MATERIAL AND METHODS: We searched PubMed for literature on live-attenuated MMR vaccination in pediatric liver transplantation (LT). RESULTS: Nine prospective observational studies and three retrospective case series were identified in which at least 833 doses of measles vaccine were administered to 716 liver transplant children receiving IST. In these selected patients, MMR vaccination was well tolerated and no serious adverse reactions to the vaccine were observed. In addition, an immune response to the vaccine was demonstrated in patients receiving IST. CONCLUSION: Due to inadequate vaccine protection in this high-risk group, maximum efforts must be made to ensure full immunization. MMR vaccination could also be considered for unprotected patients after LT receiving IST following an individual risk assessment, as severe harm from live vaccines after liver transplantation has been reported only very rarely. To this end, it is important to establish standardized and simple criteria for the selection of suitable patients and the administration of the MMR vaccine to ensure safe use.

Live Vaccine and Varicella Postexposure Prophylaxis in Pediatric Liver Transplant Recipients: A Survey of Practice in Australia and New Zealand.

BACKGROUND: Administration of live vaccines following liver transplant (LT) has historically not been recommended due to concerns regarding risk of vaccine-attenuated disease. However, there is evidence suggesting that in select transplant recipients live vaccinations can be administered safely. Studies in other regions have indicated that despite this evidence many clinicians remain hesitant to administer live vaccinations. METHOD: A REDCap survey was distributed to gastroenterologists, pediatricians, and infectious diseases physicians at pediatric centers across Australia and New Zealand via email between September and November 2023. The survey included a series of questions regarding live vaccine and varicella postexposure prophylaxis (PEP) practices in pediatric LT recipients and barriers to live vaccine administration in this cohort. RESULTS: There was a total of 16 responses to the survey, from 10 different pediatric centers, including 10/11 pediatric gastroenterology centers and all four pediatric LT centers in the region. Only 31% (5/16) of respondents (from 3/10 different centers) offer live vaccines. The main barrier to live vaccine administration was clinician reluctance and the main reason for not offering live vaccines was insufficient safety data. Sixty-nine percent (11/16) of respondents take vaccination status and/or serology into account when deciding whether to offer varicella PEP to this cohort. Respondents universally offer varicella zoster immunoglobulin as PEP, though 31% (5/16) also offer antiviral medication. CONCLUSIONS: Many clinicians in our region remain hesitant to provide live vaccines to pediatric LT recipients, with concerns regarding insufficient safety data. Updated local guidelines may help to address this.

Phase III, open-label, single-arm study of a new MMR vaccine (JVC-001); measles AIK-C, mumps RIT 4385, rubella Takahashi, as a second vaccine dose in healthy Japanese children aged 5-6 years.

PURPOSE: This Phase III, multicenter, open-label, single-arm study evaluated the safety and immunogenicity of the measles-mumps-rubella (MMR) combined vaccine, JVC-001, as a second MMR vaccination. METHODS: Healthy Japanese children aged 5-6 years received a single dose of JVC-001 following a first measles, mumps, and rubella vaccination (measles-rubella bivalent and mumps monovalent vaccine [Hoshino or Torii strain] or JVC-001) or the MMR vaccine received between ages 1 to <4 years. Immunogenicity was evaluated using antibody titers before and after vaccination (Day 1/Day 43). The primary endpoint was the seroprotection rate of antibody titers against each virus; geometric mean titer (GMT) was also evaluated. Adverse events (AEs) and adverse drug reactions (ADRs) were monitored. RESULTS: One-hundred participants completed the study. The seroprotection rate of antibody titers against measles, rubella, and mumps virus (genotype D) were 100.0 % (95 % confidence interval [CI] 96.4 %, 100.0 %), 100.0 % (95 % CI 96.4 %, 100.0 %), and 100.0 % (95 % CI 96.3 %, 100.0 %), respectively. GMT (fold) increases (Day 1 to Day 43) were 16.0 to 55.7 for measles virus, 35.5 to 99.0 for rubella virus, and 25.7 to 89.5 for mumps virus (genotype D). Solicited ADRs occurred in 40.0 % of participants (injection site, 34.0 %; systemic, 13.0 %). CONCLUSIONS: The second MMR vaccination with JVC-001 demonstrated sufficient antibody coverage against all three viruses; the safety profile was tolerable. CLINICAL TRIAL REGISTRATION: jRCT2080225022.

Molecular characterization of Mumps virus genotype C detected from Dibrugarh district of Assam, India.

Background & objectives Mumps, a contagious disease caused by the mumps virus (MuV) involves parotid gland inflammation, with potential complications affecting organs other than the parotid glands and central nervous system. Despite successful vaccination, a resurgence of mumps occurred, raising concerns about vaccine effectiveness. This study aimed to examine the entire genome of a representative MuV genotype C from Dibrugarh, Assam, and compare it with references to detect genetic variations in the circulating strain. Methods Representative MuV genotype C from our published study was subjected to whole genome sequencing. MuV genome was analyzed against the reference genome and vaccine strains before being subjected to mutational profiling, N-glycosylation site determination, and phylogenetic analysis. The Immune Epitope Database was used for epitope screening, and selected epitopes were mapped against Assam MuV for conservancy studies. Results Mutational analysis of Assam MuV with WHO (World health Organization) reference, vaccine strains Jeryl Lynn (Genotype A), and L Zagreb (Genotype N) showed variations in seven genes. Phylogenetic analysis established Assam MuV as genotype C. Epitope conservancy analysis highlighted subtle variations in experimentally determined T-cell epitopes for HN and F proteins, emphasizing overall epitope stability. Interpretation & conclusions Genome sequencing has evolved into a standard and potent method for investigating and recording circulating MuV as it provides information on surveillance, mutation analysis, and transmission dynamics. Despite mumps' global effect, genomic studies are limited, particularly in north-east. Our study provides first comprehensive whole-genome report on circulating MuV genotype C in Assam. This research contributes vital genomic data, filling gaps in MuV genetic epidemiology, supporting global research, and assessing vaccine effectiveness.

Information on Measles, Mumps and Rubella Vaccine in the Copenhagen School Health Records Register.

BACKGROUND: The Copenhagen School Health Record Register (CSHRR) includes health information from school examinations and is now updated with information on measles, mumps and rubella vaccines for the cohorts born from 1977 to 1994. AIM: The aim of this study is to provide a comprehensive description and validation the newly digitised vaccine information in the CSHRR. METHODS: We describe the data collection and the newly digitalised information in the CSHRR. We investigate the extent to which the full CSHRR population is representative of Copenhagen and the entire Danish population. Furthermore, we explore how the registry information on vaccination uptake based on reimbursement data matches the vaccine information obtained from CSHRR for the period during which both data are available. RESULTS: The CSHRR population matches closely the complete population of all schoolchildren in Copenhagen, and information on vaccine uptake in CSHRR matches with vaccine registry data for later cohorts. However, a sizable proportion of the immigrant children in the CSHRR have missing information on vaccination. Removing children who have had no additional immunisations enhances data quality. CONCLUSIONS: The CSHRR covers a large share of the Danish population and includes detailed vaccine information. By linking the data to other registry data, the updated CSHRR is valuable resource for future research.

The impact of temperature, humidity and closing school on the mumps epidemic: a case study in the mainland of China.

BACKGROUND: To control resurging infectious diseases like mumps, it is necessary to resort to effective control and preventive measures. These measures include increasing vaccine coverage, providing the community with advice on how to reduce exposure, and closing schools. To justify such intervention, it is important to understand how well each of these measures helps to limit transmission. METHODS: In this paper, we propose a simple SEILR (susceptible-exposed-symptomatically infectious-asymptomatically infectious-recovered) model by using a novel transmission rate function to incorporate temperature, humidity, and closing school factors. This new transmission rate function allows us to verify the impact of each factor either separately or combined. Using reported mumps cases from 2004 to 2018 in the mainland of China, we perform data fitting and parameter estimation to evaluate the basic reproduction number  R 0 . As a wide range of one-dose measles, mumps, and rubella (MMR) vaccine programs in China started only in 2008, we use different vaccination proportions for the first Stage I period (from 2004 to 2008) and the second Stage II period (from 2009 to 2018). This allows us to verify the importance of higher vaccine coverage with a possible second dose of MMR vaccine. RESULTS: We find that the basic reproduction number  R 0  is generally between 1 and 3. We then use the Akaike Information Criteria to assess the extent to which each of the three factors contributed to the spread of mumps. The findings suggest that the impact of all three factors is substantial, with temperature having the most significant impact, followed by school opening and closing, and finally humidity. CONCLUSION: We conclude that the strategy of increasing vaccine coverage, changing micro-climate (temperature and humidity), and closing schools can greatly reduce mumps transmission.

Cytokine Storm Syndrome Associated with Hemorrhagic Fever and Other Viruses.

A wide variety of infections can trigger cytokine storm syndromes including those caused by bacteria, viruses, fungi and parasites. The most frequent viral trigger is Epstein-.Barr virus which is covered in Chapter 16. CSS associated with COVID-19 is also discussed separately (Chapter 22). This chapter will focus on other viruses including the hemorrhagic fever viruses, influenza, parainfluenza, adenovirus, parvovirus, hepatitis viruses, measles, mumps, rubella, enterovirus, parechovirus, rotavirus, human metapneumovirus and human T-lymphotropic virus. The published literature consists of many single case reports and moderate-sized case series reporting CSS, in most circumstances meeting the 2004 diagnostic criteria for hemophagocytic lymphohistiocytosis (HLH). There is no published clinical trial evidence specifically for management of HLH associated with these viruses. In some situations, patients received supportive therapy and blood product transfusions only but in most cases, they were treated with one or more of intravenous corticosteroids, intravenous immunoglobulin and/or etoposide. These were successful in many patients although in significant numbers progression of infection to CSS was associated with mortality.

Activation of PTH1R alleviates epididymitis and orchitis through Gq and ß-arrestin-1 pathways.

Inflammation in the epididymis and testis contributes significantly to male infertility. Alternative therapeutic avenues treating epididymitis and orchitis are expected since current therapies using antibiotics have limitations associated to side effects and are commonly ineffective for inflammation due to nonbacterial causes. Here, we demonstrated that type 1 parathyroid hormone receptor (PTH1R) and its endogenous agonists, parathyroid hormone (PTH) and PTH-related protein (PTHrP), were mainly expressed in the Leydig cells of testis as well as epididymal epithelial cells. Screening the secretin family G protein-coupled receptor identified that PTH1R in the epididymis and testis was down-regulated in mumps virus (MuV)- or lipopolysaccharide (LPS)-induced inflammation. Remarkably, activation of PTH1R by abaloparatide (ABL), a Food and Drug Administration-approved treatment for postmenopausal osteoporosis, alleviated MuV- or LPS-induced inflammatory responses in both testis and epididymis and significantly improved sperm functions in both mouse model and human samples. The anti-inflammatory effects of ABL were shown to be regulated mainly through the Gq and ß-arrestin-1 pathway downstream of PTH1R as supported by the application of ABL in Gnaq± and Arrb1-/- mouse models. Taken together, our results identified an important immunoregulatory role for PTH1R signaling in the epididymis and testis. Targeting to PTH1R might have a therapeutic effect for the treatment of epididymitis and orchitis or other inflammatory disease in the male reproductive system.