Measles

According to the US Centers for Disease Control and Prevention (CDC, 2012), approximately 30% of reported symptomatic measles cases have one or more complications. The most important complications are: otitis media (occurring in approximately 10% of infected cases), encephalitis (0.1% of cases), and post-infectious encephalomyelitis (0.1–0.3% of cases). Other complications of acute measles include pneumonia (5–6% of untreated cases; Kabra, 2008; CDC, 1991) and diarrhoea (8%) (CDC, 2012). Convulsions are also a relatively frequent complication (5% of cases; Miller, 1978). Complications during pregnancy occur in up to 30% of women with severe measles (Atmar, 1992).

Complications occurring during the acute phase of the disease may overlap and cannot be treated as independent. Two health states were therefore used in our model: complicated and uncomplicated. We derived the risk of complications from data reported to TESSy between 2006 and 2013. Given the high number of cases notified to TESSy without information on complications and in order to account for this uncertainty we included two scenarios. We estimated the proportion of cases reported as uncomplicated out of the number of known cases as 57.24% (excluding cases for which complications were reported as unknown or left blank). We then added the uncomplicated cases to the unknown and blank and obtained the total number 88.64% (assuming that all unknown and blank cases were uncomplicated).

In the model, the rare permanent disabilities due to otitis media, encephalitis, post-infectious encephalomyelitis and subacute sclerosing panencephalitis (SSPE) (van Steenbergen, 2006) are treated as distinct sequelae.

Otitis media and permanent disability due to otitis media

The health state otitis media occurs in around one in ten cases of acute measles and can result in permanent hearing loss (CDC, 2011). The probability of developing permanent disability due to otitis media is 0.01% (CDC, 1991) of all cases of otitis media, therefore the overall risk of developing a permanent disability has been set to 0.001%.

Encephalitis and permanent disability due to encephalitis

Encephalitis occurs in approximately 0.1% of acute symptomatic cases (Weissbrich, 2003; Beutels, 2002; Miller, 1957). Long-term sequelae of measles encephalitis are reported to occur in 20–30% of measles-related encephalitis cases (Beutels, 2002; Filia, 2007); therefore the transition probability for the health outcome ‘permanent disability due to encephalitis’ was set to 0.02-0.033%.

Encephalitis of the delayed type (Barthez Carpentier, 1992) can occur after acute illness in immunocompromised patients and may occur after asymptomatic infection (Kidd, 2003). Because of the specific population affected, and its relative rarity, the outcome tree was not modified accordingly.

Post-infectious encephalomyelitis (PIE) and permanent disability due to PIE

Post-infectious encephalomyelitis occurs in 1–3 per 1 000 infected persons, usually three to ten days after the onset of rash. Higher rates of PIE due to measles occur in adolescents and adults than in school-aged children (Perry & Halsey, 2004). The condition is associated with demyelination and is thought to have an autoimmune basis. A total of 33% of those afflicted with PIE who survive have lifelong neurological sequelae, including severe retardation, motor impairment, blindness and sometimes hemiparesis (Perry & Halsey, 2004). The transition probability in the model for developing the health outcome ‘permanent disability due to PIE’ was set to the range 0.033–0.1%.

Subacute sclerosing panencephalitis (SSPE)

On average, the symptoms of SSPE begin seven to ten years after measles infection, but they can appear anytime from one month to 27 years after infection (CDC, 2012).

Various estimates are available for the proportion of cases that develop the SSPE health outcome. SSPE is observed at a rate of 1 per 10 000–20 000 (Weissbrich, 2003; Takasu, 2003; Bellini, 2005; Garg, 2008). In children who have previously had natural measles, the risk of developing SSPE is between 0.6 and 2.2 per 100 000 cases (Hosoya, 2006). Other estimates include: one SSPE case in every 100 000 cases of measles (Rezende, 1989); 4–11 cases of SSPE per 100 000 cases of measles (CDC, 2009); one in every 25 000 measles infections (Miller, 2004); one in 8 000 for children under two years (Miller, 1992; 2004) and a 16-fold greater risk for those infected under one year of age compared with those over five years (Miller, 1992). The risk of developing SSPE is known to be age-specific (Beutels, 2002; Farrington, 1991; Miller, 2004; CDC, 2012).Therefore, transitional probabilities in the model were also specified as age-dependent (see Table 3) (Beutels, 2002). In the model, the duration for this health outcome was specified as one to two years (CDC, 2012). In the model the transition probability from SSPE to death was set to 100%.

Case fatality proportion

Measles is fatal in approximately 0.05–0.1% of cases (Wolfson, 2007; Lozano, 2012). The risk of death is higher among young children and adults (CDC, 2012). According to CDC (CDC, 2012), the most common causes of death are pneumonia in children and acute encephalitis in adults, but due to the lack of specific data for different age groups we applied the same CFP for all the same age groups.

Model input summary

Table 1. Transition probabilities used in the outcome tree

Health outcome
(Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Symptomatic infection

 

(Complicated)

(Uncomplicated)

 

 

11.36-42.76%

57.24-88.64%

 

TESSy, 2006–2013

Permanent disability following otitis media

 

0.001%

CDC, 1991

Permanent disability following encephalitis

 

0.02–0.033%

Beutels, 2002; Filia, 2007

Permanent disability following PIE

 

0.033–0.1%

Perry & Halsey, 2004

SSPE

 

See Table 3

Beutels, 2002

Fatal cases following SSPE

 

100%

 

Fatal cases following symptomatic infection

 

0.05–0.1%

Wolfson, 2007; Lozano, 2012

Table 2. Disability weights and duration

Health outcome (Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source

Symptomatic infection

(Complicated)

(Uncomplicated)

 

 

0.125 (0.104-0.152)

0.051 (0.039-0.06)

 

 

Infectious disease, acute episode, severe

Infectious disease, acute episode, moderate

0.03

Kwong, 2012

Permanent disability due to otitis media

0.008-0.103

From lowest to highest hearing loss related DWs

Remaining life expectancy

 

Permanent disability due to encephalitis

0.054-0.425

From lowest to highest Motor plus cognitive impairments related DWs

Remaining life expectancy

 

Permanent disability due to PIE

0.054-0.425

From lowest to highest Motor plus cognitive impairments related DWs

Remaining life expectancy

 

Latency period before SSPE

0

 

0.082–27

CDC, 2012

SSPE

0.276 (0.088-0.543)

From Phase 1 to Phase 3 (median is Phase 2) of subacute sclerosing panencephalitis related DWs

1–2

CDC, 2012

Table 3. Transition probabilities subacute sclerosing panencephalitis (SSPE)

Age

%

0-4

0.0081

5-9

0.0011

≥10

0.0010

References

Barthez Carpentier MA, Billard C, Maheut J, Jourdan ML, Degenne D, Ruchoux MM, et al. Acute measles encephalitis of the delayed type: neuroradiological and immunological findings. Eur Neurol. 1992;32(4):235-7.

Bellini WJ, Rota JS, Lowe LE, et al (2005). Subacute sclerosing panencephalitis: More cases of this fatal disease are prevented by measles immunization than previously recognized. J Infect Dis 192:1686–1693.

Beutels P, Van Damme P, Van Casteren V, Gay NJ, De Schrijver K, Meheus A. The difficult quest for data on "vanishing" vaccine-preventable infections in Europe: the case of measles in Flanders (Belgium). Vaccine. 2002 Oct 4;20(29-30):3551-9.

Centers for Disease Control (CDC). Measles: United States, 1990. MMWR Morb Mortal Wkly Rep 1991;40:369–372.

Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Atkinson W, Wolfe S, Hamborsky J, McIntyre L, eds. 11th ed. Washington DC: Public Health Foundation, 2009

Centers for Disease Control and Prevention (CDC). The Pink Book: Course Textbook - 12th Edition Second Printing (May 2012).

Farrington CP. Subacute sclerosing panencephalitis in England and Wales: transient effects and risk estimates. Stat Med 1991;10:1733–1744;

Filia A, Brenna A, Panà A, Maggio Cavallaro G, Massari M, Ciofi degli Atti LM. Health burden and economic impact of measles-related hospitalizations in Italy in 2002–2003. BMC Public Health. 2007; 7: 169

Garg RK (2008). Subacute sclerosing panencephalitis. J Neurol 255(12):1861–1871.

Haagsma JA, Maertens de Noordhout C, Polinder S, Vos T, Havelaar AH, Cassini A, Devleesschauwer B, Kretzschmar ME, Speybroeck N, Salomon JA. Assessing disability weights based on the responses of 30,660 people from four European countries. Population Health Metrics 2015; 13: 10

Hosoya M. Measles encephalitis: direct viral invasion or autoimmune-mediated inflammation? Intern Med. 2006;45(14):841-2.

Kabra SK, Lodha R, Hilton DJ. Antibiotics for preventing complications in children with measles. Cochrane Database of Systematic Reviews 2008, Issue 3. Art. No.: CD001477. DOI: 10.1002/14651858.CD001477.pub3.

Kwong JC, Ratnasingham S, Campitelli MA, Daneman N, Deeks SL, et al. (2012) The Impact of Infection on Population Health: Results of the Ontario Burden of Infectious Diseases Study. PLoS ONE 7(9): e44103. doi:10.1371/journal.pone.0044103

Lozano R, Naghavi M, Foreman K, Lim S, Shibuya K, Aboyans V, et al. (Dec 15, 2012). Global and regional mortality from 235 causes of death for 20 age groups in 1990 and 2010: a systematic analysis for the Global Burden of Disease Study 2010. Lancet 380 (9859): 2095–128

Miller HG, Stanton JB, Gibbons JL. Acute disseminated encephalomyelitis and related syndromes. British medical journal.1957 Mar 23;1(5020):668-72

Miller CL. Severity of notified measles. British Medical Journal. 1978; 1(6122): 1253-1255.

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 Dec;89(12):1145-8.

Murray CJL, Lopez AD, editors. The global burden of disease: a comprehensive assessment of mortality and disability from diseases, injuries, and risk factors in 1990 and projected to 2020. Cambridge: Harvard University Press, 1996.

Rezende MA. Nursing care and the neurological sequelae of measles. Revista da Escola de Enfermagem USP. 1989 Apr;23(2):141-8.

Stein CE, et al, The Global Burden of Measles in the Year 2000—A Model that Uses Country-Specific Indicators. Journal of Infectious Diseases 2003; 187(Suppl 1):S8–14.

Takasu T, Mgone JM, Mgone CS, et al (2003). A continuing high incidence of subacute sclerosing panencephalitis (SSPE) in the eastern highlands of Papua New Guinea. Epidemiol Infect 131:887–898.

Tishler M, Abramov AL. Liver involvement in measles infection of young adults. Isr J Med Sci. 1983 Sep;19(9):791-3.

Wolfson LJ, Strebel PM, Gacic-Dobo M, Hoekstra EJ, McFarland JW, et al. (2007) Has the 2005 measles mortality reduction goal been achieved? A natural history modelling study. Lancet 369: 191–200

Zhou F, Reef S, Massoudi M, Papania MJ, Yusuf HR, Bardenheier B, et al. An Economic Analysis of the Current Universal 2-Dose Measles-Mumps-Rubella Vaccination Program in the United States. The Journal of Infectious Diseases. 2004 May 1;189 Suppl 1:S131-45.