|Ahead of print
SSPE in children younger than 3 years: A case report and systematic review of clinical manifestation and outcome
Neeraj Kumar, Shweta Pandey, Ravi Uniyal, Imran Rizvi, Hardeep Singh Malhotra, Ravindra Kumar Garg
Department of Neurology, King George’s Medical University, Lucknow, Uttar Pradesh, India
|Date of Submission||05-Oct-2020|
|Date of Decision||10-Jan-2021|
|Date of Acceptance||11-Feb-2021|
|Date of Web Publication||11-Oct-2021|
Department of Neurology, King George’s Medical University, Lucknow, Uttar Pradesh.
Source of Support: None, Conflict of Interest: None
| Abstract|| |
Subacute sclerosing panencephalitis (SSPE) is typically observed in school-going children, adolescents, and young adults. Herein, we report a 3-year-old boy of SSPE and systematically review all such reported cases (age ≤3 years). We searched PubMed database on June 16, 2020 with “English language & Human only” restrictions. Eligible publications were screened and retrieved by three authors (NK, SP, and RU). Variables like author, year of publication, country, age of onset, sex, duration of illness, immunization, history of measles, clinical presentation, neuroimaging, treatment, and outcome were extracted. Neurological outcome was assessed in terms of improvement, static course or death. The defined search criteria resulted in 791 manuscripts (1951 to June 16, 2020). Only 47 manuscripts were eligible for data extraction. Seventy cases were retrieved. The mean age of onset was 26.34 months. The M:F ratio was 3.2:1. Turkey (19 cases), India (10 cases), and Japan (10 cases) collectively comprised more than half cases of SSPE. Only six children were immunized, 17 have no measles immunization, and the rest 47 had insufficient immunization records. Preceding history of measles was present in 27 cases. Most patients presented in stage II/III with altered sensorium, myoclonic jerks, and seizures. The most common reported outcome was death (18/70) followed by vegetative state (10/70). The absence of measles vaccination is frequently associated with childhood SSPE. Early measles vaccination may prevent SSPE in toddlers. Perinatal measles infection results in short onset latency and fulminant course. Outcome was not good in reviewed age group of ≤3 years.
Keywords: Measles, myoclonus, subacute sclerosing panencephalitis
|How to cite this URL:|
Kumar N, Pandey S, Uniyal R, Rizvi I, Malhotra HS, Garg RK. SSPE in children younger than 3 years: A case report and systematic review of clinical manifestation and outcome. J Pediatr Neurosci [Epub ahead of print] [cited 2023 May 30]. Available from: https://www.pediatricneurosciences.com/preprintarticle.asp?id=327902
| Introduction|| |
Subacute sclerosing panencephalitis (SSPE) is a chronic inflammatory disorder of the brain that is caused by a persistent infection with mutated measles virus. SSPE is clinically characterized by progressive mental decline, periodic myoclonic jerks, and deteriorating motor functions that ultimately culminate into a vegetative state. Death is inevitable in almost all the cases.
SSPE is a commonly encountered disease in poor and resource-constrained countries. The WHO has estimated its incidence to be approximately 4–11 cases per 100 000 cases of measles. Measles infection acquired very early in life is associated with a much higher risk (18 per 100 000 cases) of SSPE, and a risk as high as 27.9 SSPE cases per 100 000 cases of measles has been reported. In western countries, including those with complete measles vaccination coverage, SSPE cases are generally observed after an outbreak of measles. In Georgia, USA, there were 8377 and 11,495 measles cases during the 2004–2005 and 2013–2015 outbreaks, respectively. Sixteen SSPE cases in USA were observed between 2008 and 2017. Eleven (92%) of 12 SSPE cases with a known history of measles had infection at or less than 2 years of age. The overall estimate of SSPE risk (based on 8377 reported cases of measles) was 1 per 1396 cases of measles.
Generally, SSPE is reported in school-going children, adolescents, and young adults. We, hereby, present an atypical case of SSPE in a 3-year-old child and further analyze the course and outcome of SSPE in children up to 3 years of age.
| Case Report|| |
A 3-year-old boy presented with walking difficulty, recurrent falls, and generalized tonic-clonic seizures persisting for the last 1 month. The patient was fully vaccinated and never had measles in early childhood. The patient was born out of a normal uneventful full-term delivery. He had attained normal milestones so far, and his general examination was normal. Neurological examination revealed severe cognitive decline. The patient suffered from recurrent generalized myoclonus occurring at regular intervals [Video 1], failed to maintain posture, and had recurrent falls. Fundus examination was normal, and the motor and sensory examinations did not reveal any abnormality. All blood hematological and biochemical parameters were normal. Cerebrospinal fluid examination was normal with cell count 5 cells per mm3 (all lymphocytes), protein level 48 mg/dL, and glucose 50 mg/dL. Anti-measles antibody titer (41.054 NTU vs. control <9 NTU) was markedly elevated. Iron profile and serum ceruloplasmin levels were normal. Electroencephalography revealed generalized periodic spike wave discharges [Figure 1]. Magnetic resonance imaging demonstrated periventricular T2/fluid attenuation inversion recovery (FLAIR) hyperintensity [Figure 2]. Patient was treated with valproate, clonazepam, and weekly intrathecal interferon alpha. After 2 months, reduced intensity and frequency of myoclonic jerks was observed. At 2-years follow-up, he was still non-communicating and was unable to stand or walk unsupported. Now, the patient is on monthly interferon alpha with marked improvement in seizure control, myoclonic jerks, and sitting posture.
|Figure 1: Electroencephalogram showing bilateral asymmetrical, high voltage, periodic discharges|
Click here to view
|Figure 2: Magnetic resonance imaging showing periventricular and supratentorial white matter changes in T2 axial, sagittal, and coronal sequence (A, C, and D) and T2 FLAIR sequence (B)|
Click here to view
Video demonstrates recurrent generalized myoclonus occurring at regular intervals
We systematically compiled and analyzed 47 eligible publications, reporting 70 cases of SSPE, in whom symptoms appeared at the age of 3 years or less. The focus of this review was to analyze clinical presentation, course, and outcome in early age group SSPE patients. Moreover, was this group different from commonly encountered age group of SSPE patients?
| Materials and Methods|| |
We searched PubMed database on June 16, 2020 with “English language & Human only” restrictions. The following search strategy on PubMed advanced search option was done: ((((((((sspe[MeSH Terms]) OR (subacute sclerosing panencephalit*[MeSH Terms])) OR (Bosin’s disease[MeSH Terms])) OR (Dawson’s encephalitis[MeSH Terms])) OR (sclerosing leukoencephalit*, subacute[MeSH Terms])) OR (von bogaert encephalitis[MeSH Terms])) OR (inclusion body encephalitis, measles[MeSH Terms])) OR (subacute sclerosing leukoencephalit*[MeSH Terms])) AND ((child[MeSH Terms] OR Kid[MeSH Terms] OR Infant[MeSH Terms] OR Newborn[MeSH Terms])). Three authors (NK, SP, and RU) screened and retrieved articles. Two authors (NK and HSM) searched information in all articles and compiled all eligible cases. Titles, abstracts, and full texts were searched. All tables and flowchart were also searched in the selected manuscript. References were also searched for any additional eligible cases for inclusion [Figure 3].
|Figure 3: PRISMA flow diagram depicting the flow of information through the different phases of systemic review|
Click here to view
We included all studies based on mentioned search criteria. This included meta-analysis, original studies, case series, and case reports of SSPE patient with onset at ≤3 years of age.
Data were manually extracted by NK from all included articles. Variables like author, year of publication, country, age of onset (months), sex, duration of illness, immunization status, past history of measles, presenting clinical manifestation, unusual manifestation, neuroimaging, treatment, and outcome were extracted in an excel sheet and also presented in compiled form in [Table 1].,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
|Table 1: Summary of all published articles in PubMed (last searched on 16 June 2020) on subacute sclerosing panencephalitis (SSPE) in children of up to 3 years of age|
Click here to view
We focused on neurological manifestation and outcome in terms of improvement, static course, or death.
| Results|| |
The defined search criteria resulted in 791 manuscripts (1951 to June 16, 2020). Only 47 manuscripts were eligible for data extraction as per our inclusion criteria [Figure 3]. A total of 70 cases were retrieved and relevant required data were compiled [Table 1].,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
The mean age of onset was 26.34 months (range 2–36 months). Only six cases were ≤1 years of age. The male-to-female ratio was 3.2:1 (n = 51). In our review, Turkey (19 cases), India (10 cases), and Japan (10 cases) collectively comprised more than half cases of SSPE. Only six children were immunized, 17 have no measles immunization, and rest 47 cases had insufficient record regarding immunization. Preceding history of measles was present in 27 cases. Three mothers had measles during perinatal period. Most patients presented in stage II or III with altered sensorium, myoclonic jerks, and seizures. The median duration of illness before presentation was 8 weeks (mean 11.85 ± 13.4 weeks; range 1–52 weeks).
Measles IgG antibody was used as a diagnostic marker. EEG and brain imaging (CT/MRI) were also used for supporting the diagnosis of SSPE. The findings have been compiled in [Table 1].
The treatment regime varied in different publications. Interferon only (1 case), Isoprinosine only (12 cases), or both (9 cases) were used in most cases [Table 1]. Interferon alpha or interferon beta were used via intramuscular, subcutaneous, and intrathecal routes. The dosing varied from 1 to 10 million units in weekly/twice weekly/thrice weekly schedule. After intensive phase of 4–6 weeks, monthly schedule was followed. Additional use of IVIG and lamivudine have been reported too. In a study by Aydin et al., the use of subcutaneous Interferon alpha (10 mU/m2/three times a week), oral Isoprinosine (100 mg/kg/day), and lamivudine (10 mg/kg/day) resulted in better remission rate but in age group up to 3 years, the prognosis was dismal (out of 3; 2 died and 1 progressed to stage IV). Supportive use of antiepileptics was also reported.
The most common reported outcome was death (18/70) followed by vegetative state (10/70). Though static course was reported in four cases, improvement was reported in only one case. No outcome was reported in 37/70 cases.
| Discussion|| |
Globally, the average age of onset for SSPE ranges between 6 and 13 years, except in Papua New Guinea where the average age of onset is 4.9 years (range 0–56 years). SSPE usually manifests more than 6 years after childhood measles infection. In SSPE cases from Georgia, the age at presentation was between 4 and 16 years (median, 9 years). Wendorf et al. reported that the median age at presentation of SSPE, in USA, was 12 years (range, 3–35 years), and among 17 confirmed SSPE cases, only one was of 3 years of age. The latency period between measles infection and SSPE diagnosis ranged from 2.5 to 34 years (median 9.5 years). In an older study (1990–2002), Miller et al., in England and Wales, reported the age at onset of SSPE ranged from 4 to 26 years (median 12.5). Lack of measles vaccination is considered responsible for SSPE in toddlers.
Our systematic review of early onset SSPE shows that approximately 40% of early SSPE patients had measles infection in infancy. Mothers of six patients acquired measles infection during peripartum period with three patients developing measles like illness during neonatal period.
A history of prior immunization for measles was forthcoming only in six (9%) children. Most other cases were either unimmunized (17/70) or with no available data of immunization. SSPE in children with measles vaccination raises question about vaccine induced SSPE. The scientific evidence of such correlation is lacking. Other possibilities may be inadequate/inappropriate vaccination, poor immune response, and genetic susceptibility.
Yilmaz et al., in a series of nine patients, noted that SSPE patients under the age of 4 years have a poor prognosis as a result of progressive or rapidly progressive course, despite medical treatment. Our analysis revealed that the majority of these cases belonged to three countries, India, Turkey, and Japan. Failure to achieve universal immunization against measles may be a reason for early presentation. In our analysis, the duration of illness at first presentation ranged from 1week to 1year, and the majority presented within 8 weeks. Our review further indicated that the majority of patients with early onset SSPE had a rapidly progressive course. Majority of patients either died or became vegetative within 6 months, indicating an acute fulminant course [Table 1].,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
The human immune system, at birth, is relatively immature. At 6 months, infants have blood anti-measles antibody levels that are below the crucial protective threshold. In addition, measles virus cause a long-lasting immunosuppression and both innate and adaptive immune mechanisms are severely affected. Measles virus evolves many mechanisms to circumvent host’s immune system. Experiments with wild-type measles virus have demonstrated that measles infection leads to depletion of memory immune cells and subsequently immune amnesia. A premature immunity in infancy against infections along with measles virus-associated immunosuppression possibly leads to a rapid viral multiplication viral persistence in the brain resulting in fulminant SSPE.
We also reported a child with SSPE who presented at 3 years of age and had rapid progression. In this patient, treatment with weekly intrathecal interferon alpha halted the progression and increased the survival. In our review, we noted that, interferon alpha and/or oral Isoprinosine were the most commonly used treatments. Results were variable, in some cases, stabilization of disease course was noted, but in the majority, relentless progression continued [Table 1].,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,,
In conclusion, the absence of measles vaccination is frequently associated with SSPE in young children. Early measles vaccination, before 9 months of age, may help in preventing SSPE in toddlers. Strict monitoring of cold chain, vaccine quality, and administration technique should be done to prevent post-vaccination measles or SSPE. Measurement of serological titer for immune response can be explored. Perinatal measles infection may result in SSPE with a short onset latency and fulminant course. Interferon alpha with/without oral Isoprinosine may be used in the treatment of SSPE. Stabilization of disease may be achieved in some cases.
Financial support and sponsorship
Conflicts of interest
The authors report no conflict of interest
| References|| |
Garg RK, Mahadevan A, Malhotra HS, Rizvi I, Kumar N, Uniyal R. Subacute sclerosing panencephalitis. Rev Med Virol 2019;29:e2058.
World Health Organization. Weekly epidemiological record. No. 2, 2006, 81, 13-20. http://www.who.int/vaccine_safety/committee/reports/wer8102.pdf?ua=1. Accessed August 17, 2020.
Khetsuriani N, Sanadze K, Abuladze M, Tatishvili N. High risk of subacute sclerosing panencephalitis following measles outbreaks in georgia. Clin Microbiol Infect 2020;26:737-42.
Panda PK, Sharawat IK. Early-onset fulminant subacute sclerosing panencephalitis in a toddler. Indian Pediatr 2020;57:81-2.
Kasinathan A, Suthar R, Vyas S, Saini AG, Sankhyan N, Attri S. Subacute myelopathy: think beyond neuromyelitis optica spectrum disorder. Ann Indian Acad Neurol 2019;22:541-2.
] [Full text]
Khursheed A, Hota D, Bhalla K, Kaushik JS. Fulminant subacute sclerosing panencephalitis in an immunized 20-month-old Indian boy. Neurosciences (Riyadh) 2018;23:351-3.
Wendorf KA, Winter K, Zipprich J, Schechter R, Hacker JK, Preas C, et al
. Subacute sclerosing panencephalitis: the devastating measles complication that might be more common than previously estimated. Clin Infect Dis2017;65:226-32.
Dhawan SR, Sankhyan N, Vyas S, Singhi P. Fulminant early onset subacute sclerosing panencephalitis. Indian J Pediatr 2017;84:154-5.
Holt RL, Kann D, Rassbach CE, Schwenk HT, Ritter JM, Rota PA, et al
. Subacute sclerosing panencephalitis: the foothold in undervaccination. J Pediatr 2016;179:259-62.
Aulakh R, Tiwari A. Correspondence on “children with developmental disabilities in India: age of initial concern and referral for rehabilitation services, and reasons for delay in referral”. J Child Neurol 2015;30:667.
Saurabh K, Gupta R, Khare S, Sharma S. Atypical subacute sclerosing panencephalitis with short onset latency. Indian Pediatr 2013;50:244-5.
Raut TP, Singh MK, Garg RK, Naphade PU. Subacute sclerosing panencephalitis presenting as neuromyelitis optica. Case Reports 2012;2012:bcr2012006764.
Kamate M, Belludi AY, Madhusudana SN. Subacute sclerosing panencephalitis in a toddler. Indian J Pediatr 2012;79:1384-5.
Yilmaz K, Sahin DA. Midazolam or diazepam administration during electroencephalography helps to diagnose subacute sclerosing panencephalitis (SSPE). J Child Neurol 2010;25:994-9.
Hergüner MO, Altunbaşak S, Baytok V. Patients with acute, fulminant form of SSPE. Turk J Pediatr 2007;49:422-5.
Yilmaz D, Aydin OF, Senbil N, Yuksel D. Subacute sclerosing panencephalitis: is there something different in the younger children? Brain Dev 2006;28:649-52.
Simşek E, Oztürk A, Yavuz C, Kocabay K. Subacute sclerosing panencephalitis (SSPE) associated with congenital measles infection. Turk J Pediatr 2005;47:58-62.
Dasopoulou M, Covanis A. Subacute sclerosing panencephalitis after intrauterine infection. Acta Paediatr 2004;93:1251-3.
Serdaroglu G, Kutlu A, Tekgul H, Tutuncuoglu S. Subacute sclerosing panencephalitis: a case with fulminant course after ACTH. Pediatr Neurol 2004;31:67-70.
Sener RN. Subacute sclerosing panencephalitis findings at MR imaging, diffusion MR imaging, and proton MR spectroscopy. AJNR Am J Neuroradiol 2004;25:892-4.
Tepebaşili I, Caksen H, Odabaş D, Ataş B, Akbayram S. Report of two children with subacute sclerosing panencephalitis displaying an atypical clinical course. J Emerg Med 2004;26:356-9.
Aydin OF, Senbil N, Kuyucu N, Gürer YK. Combined treatment with subcutaneous interferon-alpha, oral isoprinosine, and lamivudine for subacute sclerosing panencephalitis. J Child Neurol 2003;18:104-8. doi:10.1177/08830738030180020701
Ozyürek H, Değerliyurt A, Turanli G. Subacute sclerosing panencephalitis presenting with hemiparesis in childhood: case report. J Child Neurol 2003;18:363-5. doi:10.1177/08830738030180051601
Dunand AC, Jallon P. EEG-mediated diagnosis of an unusual presentation of SSPE. Clin Neurophysiol 2003;114:737-9.
Inoue T, Kira R, Nakao F, Ihara K, Bassuny WM, Kusuhara K, et al
. Contribution of the interleukin 4 gene to susceptibility to subacute sclerosing panencephalitis. Arch Neurol 2002;59:822-7.
Cruzado D, Masserey-Spicher V, Roux L, Delavelle J, Picard F, Haenggeli CA. Early onset and rapidly progressive subacute sclerosing panencephalitis after congenital measles infection. Eur J Pediatr 2002;161:438-41.
Caksen H, Odabaş D, Ataş B. Seizures in a boy with subacute sclerosing panencephalitis during high-dose intrathecal interferon-alpha therapy. Pediatr Neurol 2002;27:75.
Anlar B, Söylemezoğlu F, Aysun S, Köse G, Belen D, Yalaz K. Tissue inflammatory response in subacute sclerosing panencephalitis (SSPE). J Child Neurol 2001;16:895-900.
Lackmann GM, Hannen M, Madjlessi F, Lenard HG, Schroten H. Rapid progressive subacute sclerosing panencephalitis in a 2-year-old child with congenital athyreosis. Clin Infect Dis 2000;31:196-9.
Tekgül H, Tutuncuoglu S, Kutukçuler N, Dizdarer G, Huseyinov A. Lymphocyte subsets and inflammatory mediators in patients with subacute sclerosing panencephalitis. J Child Neurol 1999;14:418-21.
Bancher C, Jellinger KA, Zwiauer K. Neurofibrillary tangles in the brain of a 16 month old infant. J Neurol Neurosurg Psychiatry 1996;60:231.
Zwiauer K, Forstenpointner E, Popow-Kraupp T, Hauser E, Jellinger KA. Rapid progressive subacute sclerosing panencephalitis after perinatally acquired measles virus infection. Lancet 1995;345:1124.
Khare S, Kumari S, Verghese T. Subacute sclerosing panencephalitis in Delhi. J Trop Pediatr 1994;40:326-8.
Baram TZ, Gonzalez-Gomez I, Xie ZD, Yao D, Gilles FH, Nelson MD Jr, et al
. Subacute sclerosing panencephalitis in an infant: diagnostic role of viral genome analysis. Ann Neurol 1994;36:103-8.
Miller C, Farrington CP, Harbert K. The epidemiology of subacute sclerosing panencephalitis in England and Wales 1970–1989. Int J Epidemiol 1992;21:998-1006. doi:10.1093/ije/21.5.998
Okuno Y, Nakao T, Ishida N, Konno T, Mizutani H, Fukuyama Y, et al
. Incidence of subacute sclerosing panencephalitis following measles and measles vaccination in Japan. Int J Epidemiol 1989;18:684-9.
Bakir TM, Hossain A, Ramia S, Sinha NP. Seroepidemiology of mumps, measles, and subacute sclerosing panencephalitis in Saudi Arabia. J Trop Pediatr 1988;34:254-6.
Andersson J, Ehrnst A, Larsson PH, Hedlund KO, Norrby E, Nybom R, et al
. Visualization of defective measles virus particles in cerebrospinal fluid in subacute sclerosing panencephalitis. J Infect Dis 1987;156:928-33.
Robbins SJ, Appleton B, Fiumara F, Burke C. Subacute sclerosing panencephalitis (SSPE): a report of 16 cases. Aust N Z J Med 1984;14:126-30.
Budka H, Lassmann H, Popow-Kraupp T. Measles virus antigen in panencephalitis. An immunomorphological study stressing dendritic involvement in SSPE. Acta Neuropathol 1982;56:52-62.
Derakhshan I, Massoud A, Foroozanfar N, Nikbin B, Lotfi J, Shakib N, et al
. Subacute sclerosing panencephalitis: clinical and immunologic study of 23 patients. Neurology 1981;31:177-8.
Silva CA, Rio ME, Cruz C. Protein patterns of the cerebrospinal fluid of 30 patients with subacute sclerosing panencephalitis (SSPE). Acta Neurol Scand 1981;63:255-66.
Polna I, Wyszkowski J, Kulczycki J, Szcześniak A, Abramowicz H. Prevalence of measles antibodies in patients with subacute sclerosing panencephalitis in Poland in the years 1971–1978. J Neurol 1980;224:145-53. doi:10.1007/BF00313352
Kaufman HH, Catalano LW Jr. Diagnostic brain biopsy: a series of 50 cases and a review. Neurosurgery 1979;4:129-36.
Bhettay E, Kipps A, McDonald R. Early onset of subacute sclerosing panencephalitis. J Pediatr 1976;89:271-2.
Swick HM, Brooks WH, Roszman TL, Caldwell D. A heat-stable blocking factor in the plasma of patients with subacute sclerosing panencephalitis. Neurology 1976;26:84-8. doi:10.1212/wnl.26.1.84
Ibrahim MM, Jeavons PM. The value of electroencephalography in the diagnosis of subacute sclerosing panencephalitis. Dev Med Child Neurol 1974;16:295-307.
Green SH, Wirtschafter JD. Ophthalmoscopic findings in subacute sclerosing panencephalitis. Br J Ophthalmol 1973;57:780-7.
Dayan AD, Cumings JN. An infantile case of subacute sclerosing panencephalitis with an abnormal ganglioside pattern in the brain. Arch Dis Child 1969;44:187-96.
Canelas HM, Juliäo OF, Lefèvre AB, Assis J, Tognola WA, Jorge FB, et al
. Subacute sclerosing leucoencephalitis: an epidemiological, clinical and biochemical study of 31 cases. Arquivos de Neuro-Psiquiatria 1967;25:255-68.
Campbell H, Andrews N, Brown KE, Miller E. Review of the effect of measles vaccination on the epidemiology of SSPE. Int J Epidemiol 2007;36:1334-48.
Gutierrez J, Issacson RS, Koppel BS. Subacute sclerosing panencephalitis: an update. Dev Med Child Neurol 2010;52:901-7.
Miller C, Andrews N, Rush M, Munro H, Jin L, Miller E. The epidemiology of subacute sclerosing panencephalitis in England and wales 1990-2002. Arch Dis Child 2004;89:1145-8.
Pittet LF, Posfay-Barbe KM. Increasing incidence of subacute sclerosing panencephalitis in infants: a collateral effect of under-vaccination. Clin Microbiol Infect 2020;26:662-4.
Simon AK, Hollander GA, McMichael A. Evolution of the immune system in humans from infancy to old age. Proc Biol Sci 2015;282:20143085.
Science M, Savage R, Severini A, McLachlan E, Hughes SL, Arnold C, et al
. Measles antibody levels in young infants. Pediatrics2019;144:e20190630. doi: 10.1542/peds.2019-0630.
Mina MJ, Metcalf CJ, de Swart RL, Osterhaus AD, Grenfell BT. Long-term measles-induced immunomodulation increases overall childhood infectious disease mortality. Science 2015;348:694-9.
Ayasoufi K, Pfaller CK. Seek and hide: the manipulating interplay of measlesvirus with theinnate immune system. CurrOpinVirol 2020;41:18-30.
Laksono BM, de Vries RD, Duprex WP, de Swart RL. Measles pathogenesis, immune suppression and animal models. Curr Opin Virol 2020;41:31-7.
[Figure 1], [Figure 2], [Figure 3]