Rubella

Acquired rubella

Acquired, or non-congenital rubella usually gives rise to a mild rash and asymptomatic infections are common. The rash usually begins on the face and then progresses from head to foot. It lasts about three days and is occasionally pruritic (CDC, 2009). Since up to 50% of infections may not present with a rash, many cases are not detected or reported (CDC, 2009; Ang, 2010).

Risk of complications

The most relevant complications associated with rubella virus infection include arthritis or arthralgia, thrombocytopenia, and encephalitis (Zhou, 2004). Additional, but rare complications include orchitis, neuritis, bacterial superinfection, a late syndrome of progressive panencephalitis and mild hepatitis (CDC, 2009).

Arthritis/arthralgia

Arthralgia or arthritis may occur in 30–70% of adult women who contract rubella, but it is rare in children and adult males. It rarely develops into chronic arthritis (CDC, 2009; Mandell, 1999; Johnson, 1958). An age-independent range of 30–70% was estimated as the proportion of acute infections with this complication in the model, for females only. In 11 patients with rubella arthritis studied by Yanez et al. (Yanez, 1966), the onset of arthritis occurred one to six days after the beginning of the exanthem and lasted three to 28 days (mean of nine days).

Thrombocytopenic purpura

Hemorrhagic manifestations occur in approximately one case in 3 000 – more frequently in children than in adults – of which thrombocytopenic purpura is the most common (CDC, 2009; White, 1985; Mandell, 1999; Heggie, 1969; Boyer, 1965). Based on this estimated rate of occurrence (1/3 000), the proportion with the complication was estimated as 0.03% in the model.

Acute throbocytopenic purpura is commonly seen in children aged 1–7 years, and is defined as thrombocytopenia that lasts less than six months. In cases where thrombocytopenia persists for more than six months, it is considered chronic. Chronic thrombocytopenia occurs in a very small number of children (Taghizadeh, 2008).

Encephalitis

Encephalitis occurs in one in 5 000-6 000 cases, more frequently in adults (especially in females) than in children (CDC 2009; Mandell, 1999). Notwithstanding this occurrence rate, an age/sex-independent range of 0.01–0.02% was estimated for the proportion of acute cases with this complication in the model. The severity is highly variable. Symptoms in survivors usually resolve within 1–3 weeks without neurological sequelae (Gülen, 2008; Wolinsky, 1994).

Case fatality proportion

The case fatality proportion for thrombocytopenic purpura is 2.6% (Portielje, 2001). For encephalitis the overall lethality rate is 0–50% (CDC, 2009). Therefore in the model, the case fatality proportion following the health state thrombocytopenic purpura was specified with a point estimate of 4%, and the case fatality proportion following the health state encephalitis was set to the range of 20–50%.

Congenital rubella

Symptomatic infection occurs in 100% of infected foetuses between weeks 1 and 11. During weeks 11–20, symptomatic infection occurs in 30% of foetuses. After week 20 no foetus develops any manifestation of Congenital Rubella Syndrome (CRS) (Feigin, 2004). However, occasional foetal damage (deafness only) has been observed after the twentieth week (Mandell, 1999). Up to 50% of affected foetuses may appear healthy at birth and develop central nervous system abnormalities later (Duszak, 2009). Among children with CRS, 13% have one congenital defect, 24% have two defects and 63% have three or more defects (Reef, 2000).

We did not consider any loss of quality of life before birth and therefore the disability weight and duration for the symptomatic infection was set to 0.

Risk of sequelae

Hearing impairment occurs in 60% of children with CRS, heart disease in 45%, microcephaly in 27% (Reef, 2000), cataracts in 16–25% (Bloom, 2005), mental retardation in 13–25% (Lanzieri, 2004; Reef, 2000), and retinopathy in 5% (Reef, 2000). Overall, 20–40% of CRS survivors aged 35 or older have insulin-dependent diabetes (Mandell, 1999; Duszak, 2009) and 5% of survivors aged 13–19 develop some form of thyroid disease. (Duszak, 2009). Panencephalitis is a rare, fatal, late complication. The incidence of other late complications is still unknown (Duszak, 2009).

The case fatality ratio for infants with confirmed CRS is 10% (Reef, 2000).

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

 Acquired

 

 

 

 Symptomatic infection      (Arthritis/arthralgia)      (Thrombocytopenic purpura)      (Encephalitis)  (Uncomplicated)

 

      30–70%; females only
      0.03%
      0.01–0.02%
      Remaining cases

 

 

CDC 2009, Mandell 1999, Johnson 1958

CDC 2009, White 1985
CDC 2009, Mandell 1999

Fatal cases following thrombocytopenic purpura

 

2.6%

Portielje, 2001

Fatal cases following encephalitis

 

0–50%

CDC, 2009

 Congenital

 

 

 

Permanent disability due to hearing impairment

 

60%

Reef, 2000

Permanent disability due to congenital heart defects

 

45%

Reef, 2000

Permanent disability due to microcephaly

 

27%

Reef, 2000

Permanent disability due to cataract

 

16–25%

Bloom, 2005

Permanent disability due to mental retardation

 

13–25%

Lanzieri, 2004; Reef, 2000

Permanent disability due to retinopathy

 

5%

Reef, 2000

Permanent disability due to insulin-dependent diabetes

 

20–40%

Mandell, 1999; Duszak, 2009 (aged >35 years)

Permanent disability due to thyroid gland dysfunction

 

5%

Duszak, 2009 (aged 13–19 years)

Fatal cases

 

10%

Reef, 2000

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source/assumption

Symptomatic infection

    (Uncomplicated)    (Arthritis/arthralgia)    (Thrombocytopenic purpura)      (Encephalitis)

    0.007 (0.005–0.01)

    0.344 (0.3–0.391)

    0.167 (0.134–0.201)

    0.41 (0.358–0.47)

Infectious disease, acute episode, mild

Musculoskeletal problems, generalised,moderate

Thrombocytopenic purpura

Encephalopathy - moderate

0.008

0.008–0.077

0.008–0.5

0.019–0.058

CDC, 2009

CDC, 2009
Yanez, 1996

Taghizadeh, 2008 Gülen, 2008; Wolinsky, 1994/without any neurological sequelae

Congenital

 

 

 

 

Symptomatic infection

0

 

0

 

Permanent disability due to hearing impairment

0.008–0.103

From lowest to highest hearing loss related DWs

Remaining life expectancy

 

Permanent disability due to congenital heart defects

0.052–0.173

From lowest to highest heart failure related DWs

Remaining life expectancy

 

Permanent disability due to microcephaly

0.011–0.421

From lowest to highest cognitive difficulties related DWs

Remaining life expectancy

 

Permanent disability due to cataract

0.004–0.171

From lowest to highest visual impairment related DWs

Remaining life expectancy

 

Permanent disability due to mental retardation

0.011–0.421

From lowest to highest cognitive difficulties related DWs

Remaining life expectancy

 

Permanent disability due to retinopathy

0.004–0.171

From lowest to highest visual impairment related DWs

Remaining life expectancy

 

Latency period before diabetes

0

 

35

Mandell, 1999; Duszak, 2009

Latency period before thyroid dysfunction

0

 

13–19

Duszak, 2009

Permanent disability due to insulin-dependent diabetes

0.07 (0.057–0.088)

Generic uncomplicated disease: worry and daily medication

Remaining life expectancy

 

Permanent disability due to thyroid gland dysfunction

0.07 (0.057–0.088)

Generic uncomplicated disease: worry and daily medication.

Remaining life expectancy

 

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