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.

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.

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.

Local public health response to vaccine-associated measles: case report.

BACKGROUND: The most appropriate public health approach to vaccine-associated measles in immunocompromised patients is unknown, mainly because these cases are rare and transmission of vaccine-associated measles has not been previously documented. In this case report, we describe Peel Public Health's response to a vaccine-associated measles case in an immunocompromised child in Ontario, Canada. CASE PRESENTATION: A five-year-old Canadian-born boy with a history of a hematopoetic stem cell transplant three years previously received live attenuated measles, mumps, and rubella (MMR) vaccine. Over the subsequent 7 to 14 days, he developed an illness clinically consistent with measles. There was no travel history or other measles exposure. Serology and polymerase chain reaction (PCR) testing confirmed acute measles infection. Following discussion with pediatric infectious diseases specialists, but prior to the availability of virus sequencing, it was felt that this case was most likely due to vaccine strain. Although no microbiologically confirmed secondary cases of vaccine-associated measles have been previously described, we sent notification letters to advise all contacts of measles symptoms since the likelihood of transmission from an immunocompromised patient was low, but theoretically possible. We decided to stratify contacts into immune competent and compromised and to deal with the latter group conservatively by excluding them as if they were exposed to wild-type measles because the risk of transmission of disease in this population, while presumably very low, is unknown. However, no contacts self-identified as immunocompromised and there were no secondary cases. Subsequent genotyping confirmed that this case was caused by vaccine strain measles virus. CONCLUSION: The public health approach to contact tracing and exclusions for vaccine-associated measles in immunocompromised patients is unclear. The rarity of secondary cases provides further evidence that the risk to the general public is likely extremely low. Although the risk appears negligible, exclusion and administration of immune globulin may be considered for susceptible, immunocompromised contacts of cases of vaccine-associated measles in immunocompromised patients.

Other viral infections in solid organ transplantation.

Viral infections are a major cause of morbidity and even mortality in solid organ transplant recipients. This article reviews key aspects of infections in solid organ transplant recipients from respiratory viruses, such as influenza, polyomavirus, erythrovirus B19 and measles.

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.

Emerging and reemerging infectious diseases of nonhuman primates in the laboratory setting.

Despite numerous advances in the diagnosis and control of infectious diseases of nonhuman primates in the laboratory setting, a number of infectious agents continue to plague colonies. Some, such as measles virus and Mycobacterium tuberculosis, cause sporadic outbreaks despite well-established biosecurity protocols, whereas others, such as retroperitoneal fibromatosis-associated herpesvirus, have only recently been discovered, often as a result of immunosuppressive experimental manipulation. Owing to the unique social housing requirements of nonhuman primates, importation of foreign-bred animals, and lack of antemortem diagnostic assays for many new diseases, elimination of these agents is often difficult or impractical. Recognition of these diseases is therefore essential because of their confounding effects on experimental data, impact on colony health, and potential for zoonotic transmission. This review summarizes the relevant pathology and pathogenesis of emerging and reemerging infectious diseases of laboratory nonhuman primates.

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.

Implications of vaccination and waning immunity.

For infectious diseases where immunization can offer lifelong protection, a variety of simple models can be used to explain the utility of vaccination as a control method. However, for many diseases, immunity wanes over time and is subsequently enhanced (boosted) by asymptomatic encounters with the infection. The study of this type of epidemiological process requires a model formulation that can capture both the within-host dynamics of the pathogen and immune system as well as the associated population-level transmission dynamics. Here, we parametrize such a model for measles and show how vaccination can have a range of unexpected consequences as it reduces the natural boosting of immunity as well as reducing the number of naive susceptibles. In particular, we show that moderate waning times (40-80 years) and high levels of vaccination (greater than 70%) can induce large-scale oscillations with substantial numbers of symptomatic cases being generated at the peak. In addition, we predict that, after a long disease-free period, the introduction of infection will lead to far larger epidemics than that predicted by standard models. These results have clear implications for the long-term success of any vaccination campaign and highlight the need for a sound understanding of the immunological mechanisms of immunity and vaccination.

Etiology of a suspected measles outbreak: preceding measles reduction activities in Pakistan.

OBJECTIVE: To characterize patients with suspected measles, determine the magnitude of the outbreak in selected areas, and perform laboratory testing on patients with suspected measles to confirm the etiology of the outbreak. STUDY DESIGN: Cross-sectional survey. PLACE AND DURATION OF STUDY: Islamabad and Rawalpindi in June 2006. METHODOLOGY: Survey and specimen collection from households was carried out in areas affected by rash and fever during the outbreak. Teams asked if household members had rash and fever and administered a detailed questionnaire of clinical signs and symptoms for measles for each person who reported a rash and fever episode. A sample of cases with fever, rash, and either cough, conjunctivitis, or coryza was laboratory tested for measles and rubella. RESULTS: Of 2,225 households visited, 284 individuals met the rash and fever case definition. Laboratory testing of eleven blood specimens revealed that the rash and fever outbreak was caused by rubella in 6 and measles in 2 with three equivocal results. CONCLUSION: Laboratory confirmation of suspected measles cases is essential during measles elimination activities in Pakistan and other countries with endemic rubella.

The MSMV hypothesis: measles virus and multiple sclerosis, etiology and treatment.

Multiple sclerosis (MS) is a progressive disease characterised by periods of quiescence and exacerbation. It is found more often in northern and southern climates, rather than those closer to the equator, where it is especially rare, and, therefore, cannot be considered as an autoimmune disease. We present the MSMV Hypothesis, involving novel ideas which encompass an understanding of the blood brain barrier (BBB) function, the lymphocyte population, together with the viral presence in the CNS of what we are calling the multiple sclerosis measles virus (MSMV) that is the immediate cause of MS, and which exhibits a similar immunologic response of the systemic virus. We assume that the geographical distribution of MS is related to MSMV's sensitivity to ultraviolet light and that it is feasible to assume a viral etiology for MS based on this. The methodology employed is eclectic and grounded on several differing approaches: involved are the meta-analyses of two comprehensive studies on the effects of azathioprine in the treatment of a large number of MS patients undertaken since the early 1990s, a pioneering pilot study that examined the effects of azathioprine treatment on a smaller set of patients in the late 1960s; and, finally, we also outline the results of several experiments in cell culture on two MV strains using a new drug lead that has been shown to effectively stave off the progression of MS by interfering with the normal replication process of the MSMV. In the latter case, strain Edmonston (MV-E) was employed, along with strain Halle (MV-H), which was obtained from a lymph node of a patient with subacute sclerosing panencephalitis (SSPE), which mimics various aspects of the pathology of neurological diseases, including demyelination. An analogue of a metabolite of azathioprine (ESP) was evaluated for antiviral activity against these two viral strains. The results proved positive for the MV-H infected cells as syncytia formation was reduced in a dose-dependent manner, and under protocols which avoided toxic effects, following ESP treatment ranging from 66% with 1 microg/ml and to 25% with 0.1 microg/ml. Since ESP is an analogue of the active metabolite of azathioprine, which exhibits positive outcomes when administered to MS patients, we submit that this metabolite is acting on MSMV, in a similar fashion to the action of ESP on MV-H.