Subacute sclerosing panencephalitis presenting as severe depression in an adult.

Subacute sclerosing panencephalitis (SSPE) is a fatal disorder that occurs as a rare complication of childhood measles. Symptoms typically manifest between the ages of 5 and 15. While the incidence of SSPE is declining globally, it is still prevalent in regions where measles remains common and vaccination rates are low due to poverty and lack of health education. Diagnosing SSPE can be challenging, particularly when patients exhibit unusual symptoms. A thorough clinical evaluation, including vaccination history, physical examination, electroencephalogram (EEG) and Cerebrospinal fluid (CSF) analysis, can help in making a diagnosis. We present the case of a young woman in her early 20s who initially experienced depressive symptoms, followed by myoclonus, dementia and visual impairment. The patient was ultimately diagnosed with SSPE based on characteristic EEG findings, neuroimaging results, CSF analysis and elevated serum measles antibody levels.

Pediatric Subacute Sclerosing Panencephalitis: A Narrative Review on Measles and the Future of Vaccination.

Subacute sclerosing panencephalitis is a rare complication due to persistent measles infection, characterized by cognitive and motor deterioration. Because subacute sclerosing panencephalitis is considered a potentially fatal complication of measles and usually presents in young populations, particularly those with measles infection under the age of 2 years, new approaches to implement vaccination programs must be devised to help avoid the worsening of patient outcome. Until the disease is eradicated globally, children in all regions of the world remain at risk of measles infection and its respective complications, and therefore, the vaccine is considered the optimal preventative measure. The legacy of measles virus goes beyond the immediate complications. Our study, therefore, aims to provide a comprehensive review on the updated insights into subacute sclerosing panencephalitis as a complication, as well as the extent and future considerations pertaining to vaccination programs in the pediatric population.

Vaccine Associated Measles Complicated by Suspected Measles Inclusion Body Encephalitis in a Pediatric Leukemia Patient and Stem Cell Transplant Recipient: A Focus on Clinical Evolution and Management.

BACKGROUND: Immunocompromised individuals are at increased risk for severe disease and complications from viral infections, highlighting the importance of vaccination. However, in extremely rare situations, vaccine associated viral infections can be associated with disseminated disease and complications in immunocompromised hosts. CASE: Herein, we present a case of a 1-year-old child diagnosed with acute myeloid leukemia less than 2 weeks after receiving live viral vaccines who developed acute vaccine-strain measles virus disease, later complicated by central nervous system involvement following hematopoietic stem cell transplantation. A brain biopsy specimen was positive for vaccine-strain measles virus detected by reverse transcriptase polymerase chain reaction. MANAGEMENT AND OUTCOME: She was treated with intravenous ribavirin, inosine pranobex, intrathecal interferon-alpha and donor lymphocyte infusion following measles-mumps-rubella vaccine boost. Despite these measures, the patient suffered neurologic decline and dysautonomia, expiring after compassionate extubation. Management and ideal risk mitigation strategies are discussed within the context of existing literature for this rare complication.

Functional properties of measles virus proteins derived from a subacute sclerosing panencephalitis patient who received repeated remdesivir treatments.

Subacute sclerosing panencephalitis (SSPE) is a rare but fatal late neurological complication of measles, caused by persistent measles virus (MeV) infection of the central nervous system. There are no drugs approved for the treatment of SSPE. Here, we followed the clinical progression of a 5-year-old SSPE patient after treatment with the nucleoside analog remdesivir, conducted a post-mortem evaluation of the patient's brain, and characterized the MeV detected in the brain. The quality of life of the patient transiently improved after the first two courses of remdesivir, but a third course had no further clinical effect, and the patient eventually succumbed to his condition. Post-mortem evaluation of the brain displayed histopathological changes including loss of neurons and demyelination paired with abundant presence of MeV RNA-positive cells throughout the brain. Next-generation sequencing of RNA isolated from the brain revealed a complete MeV genome with mutations that are typically detected in SSPE, characterized by a hypermutated M gene. Additional mutations were detected in the polymerase (L) gene, which were not associated with resistance to remdesivir. Functional characterization showed that mutations in the F gene led to a hyperfusogenic phenotype predominantly mediated by N465I. Additionally, recombinant wild-type-based MeV with the SSPE-F gene or the F gene with the N465I mutation was no longer lymphotropic but instead efficiently disseminated in neural cultures. Altogether, this case encourages further investigation of remdesivir as a potential treatment of SSPE and highlights the necessity to functionally understand SSPE-causing MeV.IMPORTANCEMeasles virus (MeV) causes acute, systemic disease and remains an important cause of morbidity and mortality in humans. Despite the lack of known entry receptors in the brain, MeV can persistently infect the brain causing the rare but fatal neurological disorder subacute sclerosing panencephalitis (SSPE). SSPE-causing MeVs are characterized by a hypermutated genome and a hyperfusogenic F protein that facilitates the rapid spread of MeV throughout the brain. No treatment against SSPE is available, but the nucleoside analog remdesivir was recently demonstrated to be effective against MeV in vitro. We show that treatment of an SSPE patient with remdesivir led to transient clinical improvement and did not induce viral escape mutants, encouraging the future use of remdesivir in SSPE patients. Functional characterization of the viral proteins sheds light on the shared properties of SSPE-causing MeVs and further contributes to understanding how those viruses cause disease.

Epilepsia Partialis Continua as a Sequelae of Measles Infection in Children With Hematolymphoid Malignancies.

PURPOSE: To share our clinical experience with the diagnosis and management of children with hematolymphoid malignancies presenting with epilepsia partialis continua (EPC) as a sequelae of measles infection. MATERIALS AND METHODS: In December 2022, a series of children in our hemato-oncology unit presented with focal status epilepticus with no conclusive evidence pointing toward any underlying etiology. One such child had a typical measles rash a few weeks before the onset of this focal status epilepticus. After a series of cases with a similar presentation, a clinical pattern suspicious for measles became evident. cerebrospinal fluid polymerase chain reaction was positive for measles virus with measles immunoglobin M detected in the serum. This led to the diagnosis of measles inclusion-body encephalitis in a series of children who presented with EPC over a period of 3 months. EPC is a rare manifestation of measles that is seen only in immunocompromised patients. RESULTS: Among the 18 children reported in this series, only 10 had a history of rashes. The rash was mostly transient and elicited only on retrospective history taking. Five of the 18 children who did not lose consciousness during the prolonged seizure episode survived the disease but had residual neurologic sequelae. Among the 18 children, two were unimmunized and immunization status could not be confirmed in three other children. CONCLUSION: This case series highlights the threats posed by measles infection in children with cancer who are immunosuppressed because of the underlying disease and ongoing chemotherapy. Loss of herd immunity because of declining measles immunization rates secondary to vaccine hesitancy and COVID-19 lockdown pose a greater risk of measles infection and its complications for patients with deficient immune systems.

Therapeutic mitigation of measles-like immune amnesia and exacerbated disease after prior respiratory virus infections in ferrets.

Measles cases have surged pre-COVID-19 and the pandemic has aggravated the problem. Most measles-associated morbidity and mortality arises from destruction of pre-existing immune memory by measles virus (MeV), a paramyxovirus of the morbillivirus genus. Therapeutic measles vaccination lacks efficacy, but little is known about preserving immune memory through antivirals and the effect of respiratory disease history on measles severity. We use a canine distemper virus (CDV)-ferret model as surrogate for measles and employ an orally efficacious paramyxovirus polymerase inhibitor to address these questions. A receptor tropism-intact recombinant CDV with low lethality reveals an 8-day advantage of antiviral treatment versus therapeutic vaccination in maintaining immune memory. Infection of female ferrets with influenza A virus (IAV) A/CA/07/2009 (H1N1) or respiratory syncytial virus (RSV) four weeks pre-CDV causes fatal hemorrhagic pneumonia with lung onslaught by commensal bacteria. RNAseq identifies CDV-induced overexpression of trefoil factor (TFF) peptides in the respiratory tract, which is absent in animals pre-infected with IAV. Severe outcomes of consecutive IAV/CDV infections are mitigated by oral antivirals even when initiated late. These findings validate the morbillivirus immune amnesia hypothesis, define measles treatment paradigms, and identify priming of the TFF axis through prior respiratory infections as risk factor for exacerbated morbillivirus disease.

Patients With Subacute Sclerosing Panencephalitis in Japan: A 2022 Nationwide Survey.

BACKGROUND: In Japan, the incidence of subacute sclerosing panencephalitis (SSPE) has reduced; however, the medical conditions and factors associated with disease progression remain unclear. METHODS: A nationwide survey of SSPE was conducted using a questionnaire in 2022. We conducted a descriptive analysis of the patients with SSPE in 2022 and Cox proportional hazards analyses for disease progression. We compared the patients with SSPE with those in a 2007 survey. RESULTS: A total of 37 surviving patients with SSPE were enrolled [median age: 32 years (range: 16-52 years)]. No new cases have been identified since 2017 in the survey. Jabbour stage IV was the most common stage (66.7%). The hazard ratios (95% confidence intervals) of male sex and age at the time of measles infection (years) were 2.56 (1.13-5.76) and 0.57 (0.34-0.93), respectively. Compared with those in 2007, the proportion of patients in hospitals decreased from 13.7% to 2.7%, whereas that of patients in nursing facilities increased from 17.6% to 29.7%. The proportions of patients prescribed inosine pranobex, interferon and ribavirin at the time of the survey decreased from 96.1% to 79.4%, 74.8% to 14.3% and 25.3% to 0%, respectively. The proportions of patients with gastrostomy, tracheostomy and ventilator use increased from 5.9% to 69.7%, 23.3% to 60.0% and 10.8% to 32.4%, respectively. CONCLUSIONS: Decreased measles cases in Japan reduced new SSPE cases. However, surviving patients in 2022 had advanced disease stages and needed medical care. Male sex and early measles infection were significantly associated with disease progression.

Measles Virus and the Central Nervous System: An Update.

MEASLES VIRUS AND ASSOCIATED CENTRAL NERVOUS SYSTEM: Sequelae Renee Buchanan, Daniel J. Bonthius Seminars in Pediatric Neurology Volume 19, Issue 3, September 2012, Pages 107-114 Worldwide, measles remains one of the most deadly vaccine-preventable diseases. In the United States, enrollment in the public schools requires that each child receives 2 doses of measles-containing vaccine before entry, essentially eliminating this once endemic disease. Recent outbreaks of measles in the United States have been associated with importation of measles virus from other countries and subsequent transmission to intentionally undervaccinated children. The central nervous system complications of measles can occur within days or years of acute infection and are often severe. These include primary measles encephalitis, acute postinfectious measles encephalomyelitis, measles inclusion body encephalitis, and subacute sclerosing panencephalitis. These measles associated central nervous system diseases differ in their pathogenesis and pathologic effects. However, all involve complex brain-virus-immune system interactions, and all can lead to severe and permanent brain injury. Despite better understanding of the clinical presentations and pathogenesis of these illnesses, effective treatments remain elusive.

Fatal subacute sclerosing panencephalitis in an 8-year-old male: a case report.

Subacute sclerosing panencephalitis (SSPE) is a chronic slow progressive neurodegenerative disease that is often associated with measles complications. The disease is characterized by seizures, behavioral changes, motor deficit and eventually death. In this case report we discuss the case of an 8-year-old male who developed SSPE and was presented to our hospital with a history of generalized tonic colonic convulsion followed by gait abnormality, episodes, abnormal behaviors, and cognitive regression. On clinical exploration, the child had a history of measles at 8 months of age and meningitis at 18 months. The electroencephalogram (EEG) investigation showed high amplitude spikes, with focal seizure and slowing, while the magnetic resonance imaging reveal signals synonymous with high fluid-attenuated inversion recovery (FLAIR), both of which are consistent with probable SSPE. The case was managed symptomatically; until his parents decided to take him back home, after which his condition deteriorated, and he sadly died. To the best of our knowledge, this is the first recorded case of SSPE in Mogadishu, Somalia. Hence, the need to further investigation to better understand the incidence of the disease in the population and propose better ways of managing the condition.

Rubella virus-associated necrotizing neutrophilic granuloma in a patient with common variable immunodeficiency.

Patients with inborn errors of immunity (IEI) may develop granulomas in multiple organ systems including the skin. Vaccine strain rubella virus (RuV), part of the live attenuated measles, mumps, and rubella (MMR) vaccine, has been identified within these granulomas. RuV is typically found in macrophages; however, recently neutrophils have been identified as a novel cell type infected. Here, we present a case of RuV-associated cutaneous granuloma with RuV localized to neutrophils. A 46-year-old female with common variable immunodeficiency presented with verrucous papules and crusted plaques from the right knee to the distal shin of 20 years duration, associated with prior physical trauma. Biopsy specimen showed palisaded granulomas surrounding central necrosis with scattered aggregates of neutrophils. Vaccine-derived RuV was detected by molecular sequencing in lesional skin. Fluorescent immunohistochemistry with CD206, myeloperoxidase (MPO), and RV capsid (RVC) antibodies demonstrated that RuV localized to neutrophils but not macrophages. The clinical presentation, cutaneous findings, and likely presence of RVC-positive granulocytes in bone marrow provide potential support to the evolving hypothesis of persistent RuV within neutrophils contributing to chronic granulomatous inflammation in a milieu of immune dysregulation.

A Single-Center Evaluation of Pediatric Measles Cases in Istanbul, Türkiye, in 2019.

Although measles can be prevented and eliminated by vaccination, it is a highly contagious viral disease that can lead to serious complications, disability, and death. The aim of this retrospective study was to evaluate the characteristics of measles cases in a single center. All children with clinically suspected measles who attended the Pediatric Clinic at Esenler Maternity and Child Health Hospital in Istanbul, Türkiye, between January 1 and June 30, 2019 were included in the analysis. None of the children with measles were fully vaccinated. The incidence and duration of conjunctivitis were significantly higher in the unvaccinated group than in the partially vaccinated group (P = 0.027 and P = 0.019, respectively). Unvaccinated patients had a significantly lower median leukocyte count (P = 0.019) and significantly higher median C-reactive protein level (P = 0.021). The vitamin A level and leukocyte count were moderately positively correlated (r = 0.698; P = 0.008). Children should be fully vaccinated in order to prevent measles.

Obstetric outcomes in pregnant women with subacute sclerosing panencephalitis (SSPE): a systematic review of case reports and case series.

BACKGROUND: Subacute sclerosing panencephalitis (SSPE) is a devastating brain disease caused by persistent infection by the measles virus. Several cases of SSPE in pregnant ladies have been described. This systematic review is focused on maternal and foetal outcomes among pregnant women with SSPE. METHODS: We searched four databases (PubMed, Embase, Scopus, and Google Scholar). We reviewed all relevant cases, published until 14 August 2022. The review was conducted following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The protocol was registered with PROSPERO (CRD42022348630). The search items that we used were "((Pregnancy) OR (delivery)) AND (Subacute sclerosing panencephalitis (SSPE))". Dyken's criteria were used for the diagnosis of SSPE in pregnant women. The extracted data was recorded in an Excel sheet. The Joanna Briggs Institute Critical Appraisal tool for case reports was used to assess the quality of published cases. RESULTS: We came across 19 reports describing details of 21 cases. The age of SSPE-affected women varied from 14 to 34 years (mean 23 years). In the majority (n=14), clinical manifestations were started in the antepartum period. Nine pregnant SSPE women presented with vision loss. After delivery, 13 SSPE-affected women died. On the contrary, 15 foetuses, though the majority were preterm, were alive. Five foetuses either died soon after birth or were still-born. CONCLUSION: In conclusion, SSPE in pregnancy is often missed, as it mimics eclampsia. SSPE in pregnancy usually has a devastating course. Universal early childhood measles vaccination is the only way to fight this menace.

How to differentiate skin rash in covid, mononucleosis, chickenpox, sixth disease and measles.

PURPOSE OF REVIEW: Skin rashes seen during COVID-19 usually feature maculopapular or vesicular morphology, thus mimicking cutaneous eruptions occurring in other common infectious dermatoses, such as mononucleosis, chickenpox, sixth disease and measles, with possible diagnostic mistakes. In this review article, we sought to provide a practical overview about clinical appearance of skin rashes related to SARS-CoV-2 infection. RECENT FINDINGS: The study summarizes literature evidence on clinical patterns of COVID-19-associated maculopapular or vesicular rash, with a particular emphasis on the principal points of differentiation with possible mimickers. SUMMARY: Several differences do exist between rashes due to SARS-CoV-2 infection and other viral eruptions, mainly including lesions morphology, spreading pattern, symptoms and mucosal involvement. The increase of awareness of such features among clinicians may help promptly recognize COVID-19-related exanthemas in order to take proper action to manage the infection.

The Occurrence of Acute Pancreatitis in Adult Patients during a Measles Outbreak from November 2017 to May 2018 in Southeastern Serbia.

Background and Objectives: Although it is believed that measles infections are under control, there is a global reappearance, and their treatment has become more complex as the disease is followed by a relatively high incidence of complications. This study, conducted on patients during a measles outbreak from November 2017 to May 2018, aims to evaluate a rarely reported complication of measles, acute morbilous pancreatitis (AMP), which has been reported in several cases to date. Materials and Methods: A total of 207 patients admitted and treated at the Clinic for Infectious Diseases, Clinical Center Nis, for measles infection were included in the analysis. The data collected from the patient's medical records included the demographic characteristics, disease duration, full blood, serum, and urine biochemical analysis, general measles-associated symptoms, and disease outcome. Results: According to the serum and urine amylase activity, and some clinical symptoms AMP were diagnosed in 14% (29/207) of the studied patients. These patients had significantly higher levels of ALT and vomited more frequently than the patients without AMP. Only slight differences in measles duration, changes in RBC count, and CRP levels were found between the males and females with AMP. Conclusions: Acute morbillous pancreatitis should not be underestimated as a complication, even though according to the results of our survey, it was not associated with a fatal outcome or disease severity as the course of it can be frequently rapid and fatal.

The measles epidemic in northern Kosovo and Metohija, Serbia, October 2017-August 2019.

INTRODUCTION: Measles is among the most contagious and vaccine-preventable respiratory diseases. The aim of this research was to describe the socio-demographic profile, clinical manifestations and laboratory parameters of measles patients hospitalized at Kosovska Mitrovica Clinical Centre during the 2017-2019 outbreak. METHODOLOGY: The prospective study included all patients that had contracted measles (107) who were hospitalized at Kosovska Mitrovica Clinical Centre during the outbreak. All complications that led to hospitalization were analyzed and the frequencies of complications with respect to patient age and vaccination status were recorded. RESULTS: More than half (51%) of the patients were unvaccinated. Patients' age varied statistically significantly with respect to vaccination status. Pneumonia was noted in 65% of the patients from the younger age group, compared to 32% of adults, and this difference was statistically significant. Hepatitis was a significantly more frequent complication in adults, affecting 36% of measles patients in this age group, compared to only 7% of those aged below 18 years. In the unvaccinated group, 71% pneumonia frequency was noted, compared to 11% and 35% in the vaccinated and unknown vaccination status groups, respectively. The differences in frequencies based on vaccination status were statistically significant. CONCLUSIONS: Most hospitalized patients were unvaccinated. Complications showed a significant difference with respect to the age and vaccination status of patients. Therefore, it is necessary to carry out continuous health promotion activities to raise awareness among the entire population of the importance and need for vaccination of children against measles, but also adults who have not been previously vaccinated.

Vitamin A supplementation for preventing morbidity and mortality in children from six months to five years of age.

BACKGROUND: Vitamin A deficiency (VAD) is a major public health problem in low- and middle-income countries, affecting 190 million children under five years of age and leading to many adverse health consequences, including death. Based on prior evidence and a previous version of this review, the World Health Organization has continued to recommend vitamin A supplementation (VAS) for children aged 6 to 59 months. The last version of this review was published in 2017, and this is an updated version of that review. OBJECTIVES: To assess the effects of vitamin A supplementation (VAS) for preventing morbidity and mortality in children aged six months to five years. SEARCH METHODS: We searched CENTRAL, MEDLINE, Embase, six other databases, and two trials registers up to March 2021. We also checked reference lists and contacted relevant organisations and researchers to identify additional studies. SELECTION CRITERIA: Randomised controlled trials (RCTs) and cluster-RCTs evaluating the effect of synthetic VAS in children aged six months to five years living in the community. We excluded studies involving children in hospital and children with disease or infection. We also excluded studies evaluating the effects of food fortification, consumption of vitamin A rich foods, or beta-carotene supplementation. DATA COLLECTION AND ANALYSIS: For this update, two review authors independently assessed studies for inclusion resolving discrepancies by discussion. We performed meta-analyses for outcomes, including all-cause and cause-specific mortality, disease, vision, and side effects. We used the GRADE approach to assess the quality of the evidence. MAIN RESULTS: The updated search identified no new RCTs. We identified 47 studies, involving approximately 1,223,856 children. Studies were set in 19 countries: 30 (63%) in Asia, 16 of these in India; 8 (17%) in Africa; 7 (15%) in Latin America, and 2 (4%) in Australia. About one-third of the studies were in urban/periurban settings, and half were in rural settings; the remaining studies did not clearly report settings. Most studies included equal numbers of girls and boys and lasted about one year. The mean age of the children was about 33 months. The included studies were at variable overall risk of bias; however, evidence for the primary outcome was at low risk of bias. A meta-analysis for all-cause mortality included 19 trials (1,202,382 children). At longest follow-up, there was a 12% observed reduction in the risk of all-cause mortality for VAS compared with control using a fixed-effect model (risk ratio (RR) 0.88, 95% confidence interval (CI) 0.83 to 0.93; high-certainty evidence). Nine trials reported mortality due to diarrhoea and showed a 12% overall reduction for VAS (RR 0.88, 95% CI 0.79 to 0.98; 1,098,538 children; high-certainty evidence). There was no evidence of a difference for VAS on mortality due to measles (RR 0.88, 95% CI 0.69 to 1.11; 6 studies, 1,088,261 children; low-certainty evidence), respiratory disease (RR 0.98, 95% CI 0.86 to 1.12; 9 studies, 1,098,538 children; low-certainty evidence), and meningitis. VAS reduced the incidence of diarrhoea (RR 0.85, 95% CI 0.82 to 0.87; 15 studies, 77,946 children; low-certainty evidence), measles (RR 0.50, 95% CI 0.37 to 0.67; 6 studies, 19,566 children; moderate-certainty evidence), Bitot's spots (RR 0.42, 95% CI 0.33 to 0.53; 5 studies, 1,063,278 children; moderate-certainty evidence), night blindness (RR 0.32, 95% CI 0.21 to 0.50; 2 studies, 22,972 children; moderate-certainty evidence), and VAD (RR 0.71, 95% CI 0.65 to 0.78; 4 studies, 2262 children, moderate-certainty evidence). However, there was no evidence of a difference on incidence of respiratory disease (RR 0.99, 95% CI 0.92 to 1.06; 11 studies, 27,540 children; low-certainty evidence) or hospitalisations due to diarrhoea or pneumonia. There was an increased risk of vomiting within the first 48 hours of VAS (RR 1.97, 95% CI 1.44 to 2.69; 4 studies, 10,541 children; moderate-certainty evidence). AUTHORS' CONCLUSIONS: This update identified no new eligible studies and the conclusions remain the same. VAS is associated with a clinically meaningful reduction in morbidity and mortality in children. Further placebo-controlled trials of VAS in children between six months and five years of age would not change the conclusions of this review, although studies that compare different doses and delivery mechanisms are needed. In populations with documented VAD, it would be unethical to conduct placebo-controlled trials.

Severe Pneumonitis in Omani Infants During An In-Hospital Measles Outbreak: A report of three cases.

Measles is a highly contagious infectious disease. Despite aggressive national initiatives to eradicate measles, outbreaks have occurred in recent years. We report three infants who presented to a tertiary care hospital in Muscat, Oman, in 2019 with measles and then developed pneumonitis, received intensive care treatment and made full recoveries. Infants can have an atypical presentation and develop severe symptoms. Pneumonitis is a serious complication and the management strategies are controversial. The early detection of measles and isolation of affected individuals play major roles in the elimination of measles outbreaks.

Differential health impact of intervention programs for time-varying disease risk: a measles vaccination modeling study.

BACKGROUND: Dynamic modeling is commonly used to evaluate direct and indirect effects of interventions on infectious disease incidence. The risk of secondary outcomes (e.g., death) attributable to infection may depend on the underlying disease incidence targeted by the intervention. Consequently, the impact of interventions (e.g., the difference in vaccination and no-vaccination scenarios) on secondary outcomes may not be proportional to the reduction in disease incidence. Here, we illustrate the estimation of the impact of vaccination on measles mortality, where case fatality ratios (CFRs) are a function of dynamically changing measles incidence. METHODS: We used a previously published model of measles CFR that depends on incidence and vaccine coverage to illustrate the effects of (1) assuming higher CFR in "no-vaccination" scenarios, (2) time-varying CFRs over the past, and (3) time-varying CFRs in future projections on measles impact estimation. We used modeled CFRs in alternative scenarios to estimate measles deaths from 2000 to 2030 in 112 low- and middle-income countries using two models of measles transmission: Pennsylvania State University (PSU) and DynaMICE. We evaluated how different assumptions on future vaccine coverage, measles incidence, and CFR levels in "no-vaccination" scenarios affect the estimation of future deaths averted by measles vaccination. RESULTS: Across 2000-2030, when CFRs are separately estimated for the "no-vaccination" scenario, the measles deaths averted estimated by PSU increased from 85.8% with constant CFRs to 86.8% with CFRs varying 2000-2018 and then held constant or 85.9% with CFRs varying across the entire time period and by DynaMICE changed from 92.0 to 92.4% or 91.9% in the same scenarios, respectively. By aligning both the "vaccination" and "no-vaccination" scenarios with time-variant measles CFR estimates, as opposed to assuming constant CFRs, the number of deaths averted in the vaccination scenarios was larger in historical years and lower in future years. CONCLUSIONS: To assess the consequences of health interventions, impact estimates should consider the effect of "no-intervention" scenario assumptions on model parameters, such as measles CFR, in order to project estimated impact for alternative scenarios according to intervention strategies and investment decisions.