Factors associated with measles resurgence in the United States in the post-elimination era.

There have been growing concerns of a potential re-establishment of measles transmission in the United States (US) in the years to come. This study aims to explore potential factors underlying the resurgence of measles in the US by objectively assessing the associations between annual incidence rates (AIR), case importation, vaccination status and disease outbreaks. Data on measles transmission between January 1st, 2001 and December 31st, 2019 were obtained from the national centres for disease control and prevention (CDC) surveillance databases and other published reports. Changes in incidence rates over time were assessed by binomial regression models. Of the 3874 cases of measles in the US over the study period, 3506 (90.5%, 95% CI: 89.5-91.4) occurred in US residents. The AIR per million population in US residents over this period was 0.60 (95% CI: 0.59-0.61), with an overall significant increase over time (p = 0.011). The median percentage of imported and vaccinated cases were 36% [17.9-46.6] and 15% [12.1-23.2] respectively. There was a significant decrease in the percentage of imported cases (p < 0.001) but not of vaccinated cases (p = 0.159) over time. There was a moderate and weak negative correlation between the AIR and the percentage of imported and vaccinated cases respectively (r = -0.59 and r = -0.27 respectively). On multiple linear regression there was a significant linear association between the AIR and the number of outbreaks (p = 0.003) but not with the percentage of imported cases (p = 0.436) and vaccinated cases (p = 0.692), R2 = 0.73. Strong negative and positive correlations were seen between the number of outbreaks and the percentage of imported cases (r = -0.61) and the of number states affected (r = 0.88) respectively. Despite the overall reduction in the percentage of imported cases of measles over the past two decades, pockets of internal transmission of the disease following importation via increasing number of outbreaks in unvaccinated subpopulations, reinforced by vaccine hesitancy, account for the sustained increase in measles incidence rates in the US. Controlling indigenous transmission through efficient vaccination coverage in at-risk subpopulations and among international US travellers, improved disease surveillance and rapid outbreak containment are essential in curbing the measles resurgence.

Vaccine-associated measles in a patient treated with natalizumab: a case report.

BACKGROUND: Safety of live vaccines in patients treated with immunosuppressive therapies is not well known, resulting in contradictory vaccination recommendations. We describe here the first case of vaccine-associated measles in a patient on natalizumab treatment. CASE PRESENTATION: A young female patient with relapsing-remitting multiple sclerosis on natalizumab treatment received the live attenuated measles, mumps, and rubella vaccine in preparation for a change in her treatment in favour of fingolimod, with established immunosuppressive qualities. Seven days after receiving the vaccine, our patient experienced diffuse muscle pain, fatigue, and thereafter developed a fever and then an erythematous maculopapular rash, compatible with vaccine associated measles. This was later confirmed by a positive measles RT-PCR throat swab. The patient's symptoms resolved without any sequelae. CONCLUSION: In this case report we review the immunosuppressive qualities of natalizumab and the evidence in favour and against live vaccines in patients on this treatment. Our findings reveal the insufficient understanding of the immunosuppressive effects of new immunomodulators, and thus of the safety of live vaccines in patients on such medications. While this case triggers precaution, there is insufficient evidence to conclude that natalizumab treatment could favor the onset of vaccine-associated measles.

When a viral eruption hides another one: intrafamilial outbreak of parvovirus B19 and measles virus co-infections: case report.

BACKGROUND: Despite high overall population vaccine coverage, identified clusters of persons refraining from vaccination interfere with pursued measles elimination. Clinical diagnosis of measles is often obvious due to its typical rash. Yet, febrile rashes may occur during many viral infections. Misdiagnosis of a specific primary viral infection may have severe consequences, particularly in immunocompromised subjects or pregnant women. To our knowledge, this case presentation is the first description of a measles and parvovirus B19 coinfection outbreak. Analysis of this outbreak underlines rash diagnosis difficulties and potential serology interpretation pitfalls. This case report is helpful for the clinicians in the context of measles re-emergence and proposes several methods to improve the diagnosis approach. CASE PRESENTATION: We investigated an outbreak of rash in 6 out of 8 Traveler family members presenting to Rennes University Hospital (West of France). Anti-B19V and measles IgM/IgG antibodies were measured and detection of Parvovirus B19 and measles virus genomes were done on blood and/or respiratory samples. Virological investigations finally documented 6 cases of parvovirus B19 infections, including 4 associated with measles. Interestingly, in the four coinfection cases, the rash was typical of B19V primary infection for the two children but typical of measles for the two adults. Clinical diagnosis of rash may be misleading and thorough virological investigations may be required to avoid misdiagnosis. CONCLUSIONS: This investigation first reports an intra-familial outbreak of MeV/B19V coinfections highlighting the high transmissibility of both viruses and the diagnostic challenges of dual rash-associated infections. This report also underlines the potential deleterious consequences of failure to identify measles cases, especially in a community with low vaccination coverage.

Diagnosing inborn error of immunity following the presentation of a complicated acquired infection after MMRV vaccine administration.

Live vaccine-acquired infection should attest for the occurrence of inborn errors of immunity. Autosomal recessive immunodeficiency 31B, a result of a signal transducer and activator of transcription 1 genetic mutation, results in defected interferon pathways: interferon alpha/beta and interferon gamma. These interferons are crucial for the defence against viral and mycobacterial infections. Recognition is important for preventive and therapeutic approaches. Herein, we report the presentation of a newly diagnosed 13-month-old child with immunodeficiency 31B after presenting with disseminated measles and varicella infection after Measles, Mumps, Rubella and Varicella vaccination.

Serologic screening and infectious disease consultation (IDC): Indicated in heart, lung, liver (HLL) solid organ transplants (SOT) for measles, mumps, rubella, and varicella.

BACKGROUND: Solid organ transplant (SOT) recipients are a special group of patients who require comprehensive evaluation for preventable infectious diseases before transplantation. The main aim of our study was to investigate the number of heart, lung, and liver (HLL) transplant recipients who were evaluated for their immune status against measles, mumps, rubella (MMR), and varicella (VZV). As a secondary aim, we investigated whether pre-transplant infectious disease consultation (IDC) improves vaccination rates. METHODS: This study was an institution-based retrospective analysis of HLL transplant recipients born in or after 1957 and evaluated at Mayo Clinic, FL Transplant Center between January 1st, 2016 and December 31st, 2017. Data collection was obtained from electronic medical records. The vaccination rates were compared by univariate analysis based on IDC and no ID consultation (NIDC). RESULTS: One hundred and eighty-seven (77%) of a total 242 patients received an IDC pre-transplantation. Varicella IgG levels were screened in all 187 IDC candidates. Among the 187 IDC patients, mumps, measles, and rubella IgG serologies were performed in 9 (5%), 21 (11%), and 51 (27%), respectively. Among all 242 patients, vaccines given included 2 (0.8%) MMR, 10 (4.1%) varicella and 85 (35.12%) Zostavax. Univariate analysis revealed that Zostavax was given to 76 (40.6%) pre-transplant IDC patients and only in 9 (16.7%) NIDC patients (P < .001). CONCLUSIONS: Despite the relatively high IDC rate, patients' screened numbers for MMR IgG levels were low. Results pointed out the need for MMR protocol-driven serologic screening as well as for VZV and IDC prior to transplantation to increase vaccination rates.

Is short-term exposure to ambient fine particles associated with measles incidence in China? A multi-city study.

BACKGROUND: China's rapid economic development has resulted in severe particulate matter (PM) air pollution and the control and prevention of infectious disease is an ongoing priority. This study examined the relationships between short-term exposure to ambient particles with aerodynamic diameter ≤2.5µm (PM2.5) and measles incidence in China. METHODS: Data on daily numbers of new measles cases and concentrations of ambient PM2.5 were collected from 21 cities in China during Oct 2013 and Dec 2014. Poisson regression was used to examine city-specific associations of PM2.5 and measles, with a constrained distributed lag model, after adjusting for seasonality, day of the week, and weather conditions. Then, the effects at the national scale were pooled with a random-effect meta-analysis. RESULTS: A 10µg/m3 increase in PM2.5 at lag 1day, lag 2day and lag 3day was significantly associated with increased measles incidence [relative risk (RR) and 95% confidence interval (CI) were 1.010 (1.003, 1.018), 1.010 (1.003, 1.016) and 1.006 (1.000, 1.012), respectively]. The cumulative relative risk of measles associated with PM2.5 at lag 1-3 days was 1.029 (95% CI: 1.010, 1.048). Stratified analyses by meteorological factors showed that the PM2.5 and measles associations were stronger on days with high temperature, low humidity, and high wind speed. CONCLUSIONS: We provide new evidence that measles incidence is associated with exposure to ambient PM2.5 in China. Effective policies to reduce air pollution may also reduce measles incidence.

Notes from the Field: Measles Outbreak of Unknown Source - Shelby County, Tennessee, April-May 2016.

On April 15, 2016, local public health officials in Shelby County, Tennessee, were notified of a positive measles immunoglobulin M (IgM) test for a male aged 18 months (patient A). On April 18, 2016, a second positive measles IgM test was reported for a man aged 50 years (patient B). Both patients had rash onset on April 9, 2016. The Shelby County Health Department initiated an investigation, and confirmatory testing for measles virus on oropharyngeal swabs by polymerase chain reaction (PCR) at CDC was positive for both patients. On April 21, 2016, public health officials were notified of a third suspected measles case in a female aged 7 months (patient C) who had developed a rash on April 14; PCR testing was positive. Genotyping conducted at CDC identified genotype B3 measles virus in all three cases. Genotype B3 is known to be circulating globally and has previously been associated with imported cases in the United States (1).

Many Inflammatory Bowel Disease Patients Are Not Immune to Measles or Pertussis.

BACKGROUND: Current guidelines emphasize vaccination for influenza and pneumococcus for IBD patients and the avoidance of live virus vaccines for those who are on immunosuppressive (ISS) therapy. Given the recent resurgence of measles and pertussis infections, we assessed the immune status of our IBD population in order to advise about these risks. METHODS: We prospectively collected measles and pertussis titers in our IBD patients from February 1-May 1, 2015. Immune status based on standard threshold values was determined: measles antibodies ≤0.8 antibody index (AI) = negative immunity, 0.9-1.1 AI = equivocal immunity and titers ≥1.2 AI = positive immunity. For pertussis immunity, anti-pertussis antibodies ≤5 IU/mL were considered negative immunity. Univariate analysis was performed to examine predictive factors including age, disease duration, and current medical therapies. RESULTS: A total of 122 patients' titers were assessed (77 Crohn's disease, 1 indeterminate colitis, and 45 ulcerative colitis). Sixteen (13.1 %) patients lacked detectable immunity to measles, and four (3 %) had equivocal immunity. Twelve (75 %) of the measles non-immune patients were on ISS therapy versus 65 (64 %) of 102 immune patients (OR 1.7, 95 % CI 0.5-5.9, p = 0.34). Out of 96 patients, 58 (60 %) were not immune to pertussis. Disease duration ≥10 years and age ≥50 were associated with significant lower measles titers. CONCLUSIONS: A significant number of our IBD patients lack immunity to measles, and a majority of our IBD patients do not have detectable immunity to pertussis. Importantly, the majority of the measles non-immune patients are on ISS therapy and therefore unable to receive a booster.

Preventative Care in the Patient with Inflammatory Bowel Disease: What Is New?

Patients with inflammatory bowel disease (IBD) do not receive routine preventative care at the same rate as general medical patients. This patient population is at increased risk of vaccine preventable illness such as influenza and pneumococcal pneumonia. This review will discuss health maintenance needs and preventative care issues in patients with IBD.

Measles fusion machinery is dysregulated in neuropathogenic variants.

UNLABELLED: Paramyxoviruses, including the human pathogen measles virus (MV), enter host cells by fusing their viral envelope with the target cell membrane. This fusion process is driven by the concerted actions of the two viral envelope glycoproteins, the receptor binding protein (hemagglutinin [H]) and the fusion (F) protein. H attaches to specific proteinaceous receptors on host cells; once the receptor engages, H activates F to directly mediate lipid bilayer fusion during entry. In a recent MV outbreak in South Africa, several HIV-positive people died of MV central nervous system (CNS) infection. We analyzed the virus sequences from these patients and found that specific intrahost evolution of the F protein had occurred and resulted in viruses that are "CNS adapted." A mutation in F of the CNS-adapted virus (a leucine-to-tryptophan change present at position 454) allows it to promote fusion with less dependence on engagement of H by the two known wild-type (wt) MV cellular receptors. This F protein is activated independently of H or the receptor and has reduced thermal stability and increased fusion activity compared to those of the corresponding wt F. These functional effects are the result of the single L454W mutation in F. We hypothesize that in the absence of effective cellular immunity, such as HIV infection, MV variants bearing altered fusion machinery that enabled efficient spread in the CNS underwent positive selection. IMPORTANCE: Measles virus has become a concern in the United States and Europe due to recent outbreaks and continues to be a significant global problem. While live immunization is available, there are no effective therapies or prophylactics to combat measles infection in unprotected people. Additionally, vaccination does not adequately protect immunocompromised people, who are vulnerable to the more severe CNS manifestations of disease. We found that strains isolated from patients with measles virus infection of the CNS have fusion properties different from those of strains previously isolated from patients without CNS involvement. Specifically, the viral entry machinery is more active and the virus can spread, even in the absence of H. Our findings are consistent with an intrahost evolution of the fusion machinery that leads to neuropathogenic MV variants.

Evaluation of the immune status against measles, mumps, and rubella in adult allogeneic hematopoietic stem cell transplantation recipients.

BACKGROUND: Previous studies have shown that most patients lose immunity to measles, mumps, and rubella (MMR) during long-term follow-up after allogeneic hematopoietic stem cell transplantation (HSCT), and immunizations against them have been investigated. However, these previous studies mainly targeted pediatric patients and information in adult patients is still insufficient. METHODS: We evaluated the immunity to MMR in 45 adult allogeneic HSCT patients. None of these patients received vaccination after HSCT. RESULTS: The seropositive rates at six years after allogeneic HSCT were estimated to be less than 44% for measles, less than 10% for mumps, and less than 36% for rubella. Thirteen of the 16 female patients who were 16-39 years old were negative or equivocal for rubella. Patients who developed grade II-IV acute graft-versus-host disease tended to become seronegative for measles and rubella at two years after HSCT, although the difference was not statistically significant. CONCLUSIONS: This study showed that most adult patients lost immunity to MMR after allogeneic HSCT. Although we did not evaluate the safety and efficacy of vaccination in this study, most HSCT guidelines recommend vaccination for HSCT recipients without active chronic graft-versus-host disease or ongoing immunosuppressive therapy at 24 months after HSCT. Immunization against rubella is especially important for female patients of reproductive age. Further studies will be necessary to evaluate the effect of vaccination on the antibody response in adult allogeneic HSCT recipients.

Measles in pregnancy in Lyon France, 2011.

OBJECTIVE: To identify women who had measles while being pregnant during the 2011 epidemic peak in Lyon, France, and to document maternal characteristics and fetal outcomes. METHODS: In a retrospective survey, women who had measles while being pregnant between January and December 2011 were identified from the records of the Laboratory of Virology, Hospices Civils de Lyon. Epidemiologic data, clinical characteristics, and measles outcomes were assessed. RESULTS: In total, 11 pregnant women and 2 women who had just delivered were hospitalized with measles infection in Lyon. The most severe maternal complication was pneumonia, which occurred in 4 women (30.8%). Other maternal complications included fever (11 women; 84.6%) and elevated liver enzymes (2/6 women; 33.3%). All women delivered healthy newborns. Post-exposure prophylaxis using human polyvalent immunoglobulin was initiated for three newborns whose mothers acquired measles in the immediate postpartum period. None of these newborns subsequently acquired measles, although breastfeeding was maintained. CONCLUSION: Although measles infections during pregnancy can have a deleterious effect on both mother and child, in many cases hospitalization is not required. Unnecessary admission should be avoided given the high risk of transmission of measles in an obstetrics ward.