Pertussis
Pertussis is principally toxin-mediated. Toxins paralyse the cilia of the respiratory tract cells, leading to the clinical features and complications of the disease. The clinical course of the illness is divided into three stages. The first one is the catarrhal stage, characterised by coryza, sneezing, low-grade fever and a mild, occasional cough. The cough gradually becomes more severe, and after 12 weeks, the paroxysmal stage begins, usually lasting one to six weeks. In the convalescent stage, which lasts two to three weeks, recovery is gradual and the cough becomes less paroxysmal. However, paroxysms often recur for many months after the onset of pertussis (CDC, 2009; Mandell, 1999).
Clinical manifestations of pertussis may be mild in adults and vaccinated children. Around 20% of infected persons develop mild/asymptomatic disease (Rothstein, 2005). Based on this finding, an asymptomatic proportion of 20% was specified in the model.
Risk of complications
The principal complications of pertussis are secondary infections, such as otitis media and pneumonia, neurological complications, such as seizures and encephalopathy. Other possible complications include physical sequelae of paroxysmal cough (e.g. subconjunctival haemorrhages, epistaxis, petechiae, central nervous system haemorrhage, pneumothorax and hernia) (CDC, 2009; Mandell, 1999).
Pneumonia can result from aspiration during whooping and vomiting or from impaired clearance mechanisms. It occurs in 5.2% of all patients (CDC, 2009), in up to 25% of cases reported in infants (Mandell, 1999), in 24% of individuals aged 1019 years, in 2.75.5% of those over 20 years and in 59% of those over 30 years (Rothstein, 2005).
Approximately 4% of adolescents and adults with symptomatic pertussis infection develop otitis media (De Serres, 2000).
Neurological complications of pertussis are more common among infants. In children 12 months of age or younger with pertussis in the USA (19801989), convulsions occurred in 3.0% and encephalopathy in 0.9% of cases. Encephalopathy, febrile and afebrile convulsions occur infrequently in adults with pertussis (CDC, 2009), with encephalopathy observed in 0.1% of cases during the period 19972000 (CDC, 2009).
Seizures were reported among 0.8% of all pertussis cases in the period 19972000 (CDC, 2009).
Infants with pertussis are at greater risk of complications and permanent sequelae, however complications of pertussis, including serious ones, are not uncommon in adolescents and adults, especially the elderly. Complications occur in up to 23% of patients aged 1983 years. Complications are more frequent in adults than in adolescents (28% compared to 16%) (CDC, 2009; Mandell, 1999; Rothstein, 2005).
Most complications occurring during the symptomatic acute disease phase overlap with one other. We therefore decided to aggregate all complicated cases into one health state. Risk of complications is reported to be 50% in infants (<1 year), 16% in children and adolescents and 28% in cases 20 years (CDC, 2013).
We assumed that in complete and active surveillance systems, those cases notified represent the complicated cases of pertussis. The United Kingdom has an enhanced surveillance system for pertussis where information is compiled from different sources. We therefore chose to consider the number of cases reported in the UK (20072013) as complicated. In order to estimate the proportion of complicated cases, we divided the number of cases reported in the UK by the estimated true incidence of pertussis derived from the literature: 71507 per 100 000 10 years; 46 per 100 000 <10 years (Wirsing von Konig, 2002; Diez-Domingo, 2004) (see Table 3).
Case fatality proportion
Death from pertussis is rare beyond the age of 10 years, occurring in less than 0.1% of all cases, with older adults being at greater risk than younger adults (Rothstein, 2005). Pneumonia is a leading cause of death, but in a study of 99 patients aged 5594 years who died of pertussis (Rothstein, 2005), intracranial haemorrhage was the cause of death for two of the four deaths thought to be associated with pertussis. Among patients who died, apnoea, pneumonia, seizures, and encephalopathy were reported for 58% (40 of 69), 54% (39 of 72), 21% (14 of 68), and 12% (7 of 57), respectively (Rothstein, 2005; Farizo, 1992).
The case fatality proportion in the United States between 1990 and 1996 was 0.2%. Eighty-four per cent of pertussis-related deaths occur in infants younger than six months of age (Ratnapalam, 2005).
In general, we considered that only complicated cases were at risk of dying. We used the CFP reported in the UK for deaths of infants <1 year old because of its comprehensive surveillance system, compiling data from different sources and deemed to be capturing approximately 94% of the cases in recent capture-recapture studies. There were 33 deaths due to pertussis reported to TESSy between 2007 and 2013 out of 1 791 cases. This resulted in a CFP of 1.84% which was applied to complicated cases <1 year.
We chose 0.1% of complicated cases for all other age groups.
Model input summary
Table 1. Transition probabilities used in the outcome tree
Health outcome |
Distribution of health states in health outcome |
Transition probability |
Source/assumption |
Symptomatic infection (Complicated) |
Age dependent (see Table 3) |
|
CDC, 2013 |
Fatal cases |
|
1.84% <1 yr. 0.1% ≥ 1 yr. |
TESSy Rothstein, 2005 |
Table 2. Disability weights and duration
Health
outcome |
Disability Weight (DW) (Haagsma, 2015) |
Duration |
||
DW |
Label |
In years |
Source |
|
Symptomatic infection (Complicated) (Uncomplicated) |
0.125 (0.1040.152) 0.051 (0.0390.06) |
Infectious disease, acute episode, severe Infectious disease, acute episode, moderate |
0.0770.211 |
CDC, 2009; Mandell, 1999 |
Table 3. Risk of complications
Age |
% |
||
Estimated from low true incidence |
Estimated from high true incidence |
||
0 |
28.04 |
||
01-04 |
8.04 |
||
05-09 |
5.85 |
||
10-14 |
0.35 |
2.46 |
|
15-19 |
0.39 |
2.81 |
|
20-24 |
1.05 |
7.50 |
|
25-29 |
1.59 |
11.38 |
|
30-34 |
1.92 |
13.68 |
|
35-39 |
1.45 |
10.32 |
|
40-44 |
1.84 |
13.12 |
|
45-49 |
2.23 |
15.96 |
|
50-54 |
2.00 |
14.29 |
|
55-59 |
1.68 |
11.97 |
|
60-64 |
1.20 |
8.57 |
|
65-69 |
1.48 |
10.58 |
|
70-74 |
1.24 |
8.83 |
|
75-79 |
1.30 |
9.26 |
|
80-84 |
0.91 |
6.52 |
|
85+ |
0.54 |
3.88 |
|
References
Centers for Disease Control and Prevention. Epidemiology and Prevention of Vaccine-Preventable Diseases. Atkinson W, Wolfe S, Hamborsky J, McIntyre L, eds. 11th Edition. Washington DC: Public Health Foundation, 2009.
Centers for Disease Control and Prevention. http://www.cdc.gov/pertussis/about/complications.html Last update January 2013 [accessed 25 September 2014].
De Serres G, Shadmani R, Duval B, Boulianne N, D้ry P, Douville Fradet M, et al. Morbidity of pertussis in adolescents and adults. J Infect Dis. 2000 Jul;182(1):174-9.
Diez-Domingo J, Ballester A, Baldo JM, Planelles MV, Villarroya JV, Alvarez T et al. Incidence of pertussis in persons < 15 years of age in Valencia, Spain: seroprevalence of antibodies to pertussis toxin (PT) in children, adolescents and adults. Journal of Infection (2004) 49, 242-247
Farizo KM, Cochi SL, Zell ER, Brink EW, Wassilak SG, Patriarca PA. Epidemiological features of pertussis in the United States, 1980-1989. Clin Infect Dis. 1992 Mar;14(3):708-19.
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Mandell GL, Bennet JE, Dolin R. Mandell, Douglas and Bennetts Principles and Practice of Infectious Disease 5th edition. Churchill Livingstone, 1999.
Ratnapalan S, Parkin PC, Allen U. Case 1: The deadly danger of pertussis. Paediatr Child Health. 2005 Apr;10(4):221-2
Rothstein E, Edwards K. Health burden of pertussis in adolescents and adults. Pediatr Infect Dis J. 2005 May;24(5 Suppl):S44-7.
Wirsing von Konig CH, Halperin S, Riffelmann M, Guiso N. Pertussis of adults and infants. Lancet Infect Dis 2002; 2: 744-50.