Diphtheria

Thanks to vaccination, respiratory diphtheria has almost disappeared from many European countries. In total, 85% of patients suffer from subclinical disease or turn into asymptomatic carriers (Vitek, 1998) and only an estimated 15% of infections lead to a symptomatic case. The duration of acute illness was based on the Ontario Burden of Infectious Disease Study [AC1]  (‘the Ontario Study’) [SW2] and set at 12 days (Kwong, 2012).

Risk of complications

Systemic toxicity (a toxic form of the disease with swelling of the neck) occurs in 8.1% of all diphtheria patients and may lead to complications such as myocarditis, neuropathies and renal failure (Rakhmanova, 1996). The more frequent complications of acute illness are myocarditis and polyneuropathies/nerve palsies. Other complications, such as sepsis, septic arthritis, pneumonia, otitis media, splenic and hepatic abscesses and rhinitis, were not included in the outcome tree because they are either extremely rare or mild.

Our model is based on the assumption that 8.1% of symptomatic patients would have a complicated form of the disease (Rakhmanova, 1996).

Permanent disability following myocarditis (arrhythmias)

Assuming that myocarditis represents 66.6% of the complicated diphtheria cases (Jayashree, 2006) and that 0.25% (Mandell, 1999) of these will develop permanent conduction defects (arrhythmias), the transition probability of patients with complications developing permanent cardiac disability is 0.17%.

Case fatality ratio

The US Centers for Disease Control and Prevention (US CDC) have reported a case-fatality proportion (CFP) of 5–10% for diphtheria, with higher death rates (up to 20%) among persons under five and over 40 years. The case fatality proportion has changed very little over the last 50 years (CDC, 2009).

In the model, the CFP associated with uncomplicated disease is 1% and with complicated disease 25.7% (Rakhmanova, 1996).

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

(Uncomplicated)

(Complicated)

 

91.9%

8.1%

 

Rakhmanova, 1996

Permanent disability (arrhythmias) following complicated symptomatic infection

 

0.17%

Jayashree, 2006; Mandell, 1999

Fatal cases following uncomplicated symptomatic infection

 

1%

Rakhmanova, 1996

Fatal cases following complicated symptomatic infection

 

25.7%

Rakhmanova, 1996

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source

Symptomatic infection

(Uncomplicated)

 

(Complicated)

 

0.051 (0.039-0.06)

 

0.125 (0.104-0.152)

 

Infectious disease, acute episode, moderate

Infectious disease, acute episode, severe

0.003

Kwong 2012

Permanent disability (arrhythmias) following complicated symptomatic infection

0.295 (0.258-0.343)

Cardiac conduction disorders and cardiac dysrhythmias

Remaining life expectancy

 

References

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WHO (2004). Global Burden of Disease 2004 Update: Disability weights for diseases and conditions. Geneva: WHO. Available online at: http://www.who.int/healthinfo/global_burden_disease/
GBD2004_DisabilityWeights.pdf