Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1).

PMID: 

Antiviral Res. 2002 Jan ;53(1):19-34. PMID: 11684313

Abstract Title: 

Inhibitory effects of (-)-epigallocatechin gallate on the life cycle of human immunodeficiency virus type 1 (HIV-1).

Abstract: 

Epigallocatechin gallate (EGCg), the major tea catechin, is known as a potent anti-bacterial agent. In addition, anti-tumor promoting, anti-inflammatory, anti-oxidative and antiviral activities have been reported. In the present study, we investigated possible anti-human immunodeficiency virus type-1 (HIV-1) activity of EGCg and its mechanisms of action in the viral life cycle. EGCg impinges on each step of the HIV life cycle. Thus, destruction of the viral particles, viral attachment to cells, post-adsorption entry into cells, reverse transcription (RT), viral production from chronically-infected cells, and the level of expression of viral mRNA, were analyzed using T-lymphoid (H9) and monocytoid (THP-1) cell systems, and antiviral protease activity was measured using a cell-free assay. Inhibitory effects of EGCg on specific binding of the virions to the cellular surfaces and changes in the steady state viral regulation (mRNA expression) due to EGCg were not observed. However, EGCg had a destructive effect on the viral particles, and post-adsorption entry and RT in acutely infected monocytoid cells were significantly inhibited at concentrations of EGCg greater than 1 microM, and protease kinetics were suppressed at a concentration higher than 10 microM in the cell-free study. Viral production by THP-1 cells chronically-infected with HIV-1 was also inhibited in a dose-dependent manner and the inhibitory effect was enhanced by liposome modification of EGCg. As expected, increased viral mRNA production was observed in lipopolysaccharide (LPS)-activated chronically HIV-1-infected cells. This production was significantly inhibited by EGCg treatment of THP-1 cells. In contrast, production of HIV-1 viral mRNA in unstimulated or LPS-stimulated T-lymphoid cells (H9) was not inhibited by EGCg. Anti-HIV viral activity of EGCg may thus result from an interaction with several steps in the HIV-1 life cycle.

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Primary and secondary vaccine failure are the primary reasons for inefficacy of the vaccine.

PMID: 

Vaccine. 2018 06 18 ;36(26):3721-3726. Epub 2018 May 18. PMID: 29784466

Abstract Title: 

Knowledge gaps persist and hinder progress in eliminating mumps.

Abstract: 

Mumps, a common childhood disease in the pre-vaccine era that causes swelling of the parotid salivary glands, can lead to orchitis, viral meningitis, and sensorineural deafness. While the incidence of disease decreased dramatically after the vaccine was added to standard vaccination schedules, the disease has made a substantial resurgence in recent years. As a result, it becomes critical to examine the factors involved in recurring outbreaks. Although low and incomplete vaccination coverage may be a key reason, it does not fully explain the issue due to the high rate of occurrence in populations with high vaccination coverage rates. Multiple studies suggest that waning immunity and secondary vaccine failure play a large role, the effects of which were previously masked by subclinical boosting. Significant knowledge gaps persist around the exact role and mechanism of waning immunity and demonstrate the need for more research in this area, as well as a reevaluation of mumps vaccine policy.

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This study found a 5-fold increased incidence rate for immune thrombocytopenic purpura following a dose of a measles-containing vaccine and a 10.9 increased incidence rate for aseptic meningitis following the first dose of a mumps-containing vaccine.

PMID: 

Vaccine. 2018 01 8 ;36(3):347-354. Epub 2017 May 27. PMID: 28558983

Abstract Title: 

Enhancing global vaccine pharmacovigilance: Proof-of-concept study on aseptic meningitis and immune thrombocytopenic purpura following measles-mumps containing vaccination.

Abstract: 

New vaccines designed to prevent diseases endemic in low and middle-income countries (LMICs) are now being introduced without prior record of utilization in countries with robust pharmacovigilance systems. To address this deficit, our objective was to demonstrate feasibility of an international hospital-based network for the assessment of potential epidemiological associations between serious and rare adverse events and vaccines in any setting. This was done through a proof-of-concept evaluation of the risk of immune thrombocytopenic purpura (ITP) and aseptic meningitis (AM) following administration of the first dose of measles-mumps-containing vaccines using the self-controlled risk interval method in the primary analysis. The World Health Organization (WHO) selected 26 sentinel sites (49 hospitals) distributed in 16 countries of the six WHO regions. Incidence rate ratios (IRR) of 5.0 (95% CI: 2.5-9.7) for ITP following first dose of measles-containing vaccinations, and of 10.9 (95% CI: 4.2-27.8) for AM following mumps-containing vaccinations were found. The strain-specific analyses showed significantly elevated ITP risk for measles vaccines containing Schwarz (IRR: 20.7; 95% CI: 2.7-157.6), Edmonston-Zagreb (IRR: 11.1; 95% CI: 1.4-90.3), and Enders'Edmonston (IRR: 8.5; 95% CI: 1.9-38.1) strains. A significantly elevated AM risk for vaccines containing the Leningrad-Zagreb mumps strain (IRR: 10.8; 95% CI: 1.3-87.4) was also found. This proof-of-concept study has shown, for the first time, that an international hospital-based network for the investigation of rare vaccine adverse events, using common standardized procedures and with high participation of LMICs, is feasible, can produce reliable results, and has the potential to characterize differences in risk between vaccine strains. The completion of this network by adding large reference hospitals, particularly from tropical countries, and the systematic WHO-led implementation of this approach, should permit the rapid post-marketing evaluation of safety signals for serious and rare adverse events for new and existing vaccines in all settings, including LMICs.

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Further evaluations to better understand the prevalence of mumps virus shedding among vaccinated populations are needed to guide outbreak surveillance and control.

PMID: 

MMWR Morb Mortal Wkly Rep. 2017 Dec 1 ;66(47):1307-1308. Epub 2017 Dec 1. PMID: 29190262

Abstract Title: 

Notes from the Field: Absence of Asymptomatic Mumps Virus Shedding Among Vaccinated College Students During a Mumps Outbreak – Washington, February-June 2017.

Abstract: 

[n/a]

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The Jeryl Lynn mumps vaccine virus poorly induces neutralizing antibodies.

PMID: 

Vaccine. 2017 07 13 ;35(32):3988-3994. Epub 2017 Jun 13. PMID: 28623030

Abstract Title: 

Immunogenicity of mumps virus vaccine candidates matching circulating genotypes in the United States and China.

Abstract: 

Mumps virus (MuV) causes acute infection in humans with characteristic swelling of the parotid gland. While vaccination has greatly reduced the incidence of MuV infection, there have been multiple large outbreaks of mumps virus (MuV) in highly vaccinated populations. The most common vaccine strain, Jeryl Lynn, belongs to genotype A, which is no longer a circulating genotype. We have developed two vaccine candidates that match the circulating genotypes in the United States (genotype G) and China (genotype F). We found that there was a significant decrease in the ability of the Jeryl Lynn vaccine to produce neutralizing antibody responses to non-matched viruses, when compared to either of our vaccine candidates. Our data suggests that an updated vaccine may allow for better immunity against the circulating MuV genotypes G and F.

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A report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease.

PMID: 

Clin Vaccine Immunol. 2017 Feb ;24(2). Epub 2017 Feb 6. PMID: 28003216

Abstract Title: 

Challenges in Interpretation of Diagnostic Test Results in a Mumps Outbreak in a Highly Vaccinated Population.

Abstract: 

In spite of a greatly reduced incidence rate due to vaccination, mumps outbreaks continue to occur in several areas of the world, sometimes in vaccinated populations. This article describes an outbreak in a highly vaccinated population in southwestern Ontario, Canada, and the challenges encountered in interpreting the results of diagnostic tests used in the outbreak. During the outbreak, patients were interviewed and classified according to the outbreak case definition, and specimens were collected for diagnostic testing according to Ontario guidelines. Twenty-seven individuals were classified as confirmed cases (n = 19) or suspect cases (n = 8) according to the case definition, only 9 of which were laboratory-confirmed cases: 7 confirmed by reverse transcriptase PCR (RT-PCR) and 2 by IgM serology. All 19 confirmed cases represented patients who were associated with secondary schools in the local area and had been vaccinated against mumps with one (n = 2) or two (n = 17) doses of the measles-mumps-rubella (MMR) vaccine. This is the first published report of an outbreak of mumps in Ontario in which all confirmed cases had been vaccinated against the disease. It highlights the limitations of and difficulties in interpreting current mumps diagnostic tests when used in vaccinated individuals.

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Mumps outbreaks can occur in highly vaccinated populations. Mumps should be considered in patients with parotitis regardless of vaccination status.

PMID: 

Clin Infect Dis. 2017 02 15 ;64(4):408-412. PMID: 27927872

Abstract Title: 

Mumps Outbreak Among a Highly Vaccinated University Community-New York City, January-April 2014.

Abstract: 

Background: On 14 January 2014, a vaccinated student presented with parotitis. Mumps immunoglobulin M (IgM) testing was negative and reverse-transcription polymerase chain reaction (RT-PCR) testing was not performed, resulting in a missed diagnosis and the start of an outbreak at a New York City (NYC) university.Methods: Mumps case investigations included patient interviews, medical records review, and laboratory testing including mumps serology and RT-PCR. Case patients were considered linked to the outbreak if they attended or had epidemiologic linkage to the university. Epidemiologic, clinical, and laboratory data for outbreak cases residing in NYC were analyzed.Results: Fifty-six NYC residents with mumps were identified with onset between 12 January and 30 April 2014. Fifty-three cases (95%) were university students, 1 (2%) was a staff member, and 2 (4%) had epidemiologic links to the university. The median age was 20 years (range 18-37 years). All cases had parotitis. Three cases were hospitalized, including 1 of 2 cases with orchitis. Fifty-four (96%) cases had received≥1 mumps-containing vaccine, 1 (2%) was unvaccinated due to religious exemption, and 1 (2%) had unknown vaccination status. Two of the 44 (5%) cases tested by serology were mumps IgM positive, and 27 of the 40 (68%) tested by RT-PCR were positive.Conclusions: Mumps outbreaks can occur in highly vaccinated populations. Mumps should be considered in patients with parotitis regardless of vaccination status. RT-PCR is the preferred testing method; providers should not rely on IgM testing alone. High vaccination coverage and control measures likely limited the extent of the outbreak.

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Encephalitis with seizures in 5 patients with confirmed mumps vaccine strain in cerebrospinal fluid.

PMID: 

J Neurol Sci. 2015 Feb 15 ;349(1-2):226-8. Epub 2014 Dec 18. PMID: 25542078

Abstract Title: 

Clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination.

Abstract: 

We retrospectively collected three patients with clinically mild encephalitis with a reversible splenial lesion (MERS) after mumps vaccination, and reviewed five patients, including two patients previously reported. The five patients (all males, aged 1 to 9) presented with fever, vomiting, or headache as the initial symptoms (day 0), suggesting meningitis, at 13 to 21 days after mumps vaccination. Consciousness disturbance, delirious behavior, seizures, or dysarthria was observed on days 1 to 3, which had completely resolved before day 11. Hyponatremia was observed in all patients. A cerebrospinal fluid study showed pleocytosis, and confirmed the vaccine strain genome. MRI revealed reduced diffusion in the splenium of the corpus callosum on days 2 to 4, which had completely disappeared on the follow-up studies performed on days 7-15. EEG showed high voltage slow wave in three patients, which later normalized. These findings led to a diagnosis of MERS after mumps vaccination. MERS after mumps vaccination may be more common than previously considered. MERS is suspected when a male patient after mumps vaccination presents with neurological symptoms with hyponatremia, following symptoms of aseptic meningitis, and MRI would be performed to examine the splenium of the corpus callosum.

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Another incidence of a mumps outbreak in vaccinated adults.

PMID: 

Vaccine. 2014 Jul 31 ;32(35):4393-8. Epub 2014 Jun 25. PMID: 24973734

Abstract Title: 

Mumps increase in Flanders, Belgium, 2012-2013: results from temporary mandatory notification and a cohort study among university students.

Abstract: 

INTRODUCTION: In 2012, an increase in mumps notifications occurred in Belgium, affecting young vaccinated adults. At the end of 2012, a mumps outbreak occurred at the Catholic University of Leuven KU Leuven in Flanders. We investigated the outbreak to estimate incidence, mumps vaccine effectiveness and to detect potential risk factors for the disease.METHODS: In June 2012, we set up mandatory notification in Flanders and we collected information on circulating genotypes from the National Reference Centre. We conducted a cohort study among KU Leuven students. We defined a case as self-reported parotitis, between September 2012 and March 2013. We distributed web-based questionnaires to a random sample of students. We calculated vaccine effectiveness by comparing the risks in students vaccinated twice with those vaccinated once. We estimated risk ratios (RR) to identify risk factors.RESULTS: From 16th June 2012 to 1st April 2013, 4061 mumps cases were notified to the regional public health office (30% were vaccinated once and 69% were vaccinated twice). All 16 samples collected at the KU Leuven were genotype G5. Of 717 participants of the cohort study, 38 (5%; 95%CI 4-8%) met the case-definition. All reported being vaccinated with at least one dose of mumps-containing vaccine. The incidence of mumps was 5% among those vaccinated twice and 16% among those vaccinated once (vaccine effectiveness of two doses compared to one: 68%, 95%CI -24% to 92%). The risk of mumps was lower among those vaccinated with two doses of mumps-containing vaccine≤10 years before (RR: 0.33, 95%CI 0.10-1.02) and higher among students working in a bar (RR: 3.6, 95%CI 1.8-7.0).CONCLUSIONS: Incomplete protection by two doses of mumps-containing vaccine, possible waning immunity and intense social contacts may have contributed to the occurrence of this outbreak in Flanders. Efforts to maintain high vaccination coverage with two doses remain essential. However, the reasons for low vaccine effectiveness must be further explored and additional immunological research for more immunogenic mumps vaccines is necessary.

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Description of an outbreak in 2009–2010 in the northeastern United States among a highly vaccinated population.

PMID: 

Emerg Infect Dis. 2014 Apr ;20(4):643-8. PMID: 24655811

Abstract Title: 

Epidemic of mumps among vaccinated persons, The Netherlands, 2009-2012.

Abstract: 

To analyze the epidemiology of a nationwide mumps epidemic in the Netherlands, we reviewed 1,557 notified mumps cases in persons who had disease onset during September 1, 2009-August 31, 2012. Seasonality peaked in spring and autumn. Most case-patients were males (59%), 18-25 years of age (67.9%), and vaccinated twice with measles-mumps-rubella vaccine (67.7%). Nearly half (46.6%) of cases occurred in university students or in persons with student contacts. Receipt of 2 doses of vaccine reduced the risk for orchitis, the most frequently reported complication (vaccine effectiveness [VE] 74%, 95% CI 57%-85%); complications overall (VE 76%, 95% CI 61%-86%); and hospitalization (VE 82%, 95% CI 53%-93%). Over time, the age distribution of case-patients changed, and proportionally more cases were reported from nonuniversity cities (p

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