Q fever

Q fever infection becomes symptomatic in 40% of cases (Dijkstra, 2012). Symptomatic infections are divided into two health states: uncomplicated and complicated (more severe cases) and the proportion of complications is based on the hospitalisation rate (2–5%) for Q fever (Maurin & Raoult, 1999; Raoult, 2005).

Around 1–2% of Q fever cases are fatal (ECDC, 2010). This CFR is applied to complicated cases only, based on the US Centers for Disease Control (CDC) Fact Sheet which states that ‘the case fatality ratio for hospitalized patients is under 2%’ (CDC, 2013).

Chronic Q fever

The transition probability that cases with symptomatic infections will develop chronic Q fever is set to 1.6% (1.5–2%) (van der Hoek, 2011; ECDC, 2010). Due to the lack of evidence, development of chronic Q fever was not associated with asymptomatic Q fever (ECDC, 2010). The average duration of chronic Q fever before developing symptoms is 0.5 years (0.08–1.5 years) (Fenollar, 2001) and this is included in the burden calculation as it reduces the life expectancy of later health outcomes.

Taking the duration of treatment as a proxy for the duration of chronic Q fever, we set the duration to 12–18 months (CDC, 2013) although there are studies recommending life-long treatment which could vary from one year to a person’s entire lifespan (Forland, 2012). However, we assume that symptoms due to the infection resolve during the treatment; if symptoms continue, we consider them not to be associated with the Q fever infection but with underlying conditions.

The most common manifestation of chronic Q fever is heart failure, of which a quarter of cases show conduction disorders (Marrie, 2010); other possible manifestations include vascular and pulmonary infections and chronic hepatitis (Maurin & Raoult, 1999). Therefore disability weights describing heart failure were applied.

The case fatality proportion for chronic Q fever has been estimated to be from to 5 to 50%, according to time of diagnosis and onset of treatment (ECDC, 2010).

Post-infectious fatigue syndrome

Follow-up studies after large outbreaks provide some information regarding duration and the probability of developing post-infectious fatigue syndrome. One large cohort following an outbreak in the UK used standard clinical criteria to quantify the proportion of patients developing fatigue after five years (Ayres JG, 1998) and ten years (Wildman, 2002). The first follow-up reported a larger proportion of idiopathic chronic fatigue (ICF) in Q fever cases (42.3%) than in matched controls (26%), with a difference of 16.3%. At the 10-year follow-up point, cases were matched to controls for the presence of comorbidities and hospital attendance, but there was still a higher proportion of ICF (21.6% vs. 5.4%), with a difference of 16.2%. A recent study from a Dutch outbreak indicates the proportion of patients with fatigue after 12 to 26 months to be higher (43.5%) than after five or ten years of follow-up (Morroy, 2011). Therefore, two health states were specified in order to differentiate short-term fatigue (43.5–16.2/16.3% = 27.2/27.3%) from long-term fatigue (16.2–16.3%). The short-term health state consists of clinical cases that recover within 12 to 26 months; severe cases are assumed to recover after 10 years. Regarding the sources of post-infectious fatigue syndrome (PFS), it is surprising that after 10 years the proportion of PFS is reduced to the same extent in controls as in the cases. We therefore considered the bias to be prevalent and decided to exclude PFS from the model.

Model input summary

Table 1. Transition probabilities and distributions used in the outcome tree

Health outcome
(Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Symptomatic infection

(Mild)

(Severe)

 

95–98%
2–5%

 

 

Maurin & Raoult, 1999; Raoult, 2005

Chronic Q fever

 

1.6% (1.5–2%)

van der Hoek, 2011;
ECDC, 2010

Fatal cases following symptomatic infection

 

1-2% of severe cases

ECDC, 2010

Fatal cases following chronic infection

 

5-50%

ECDC, 2010

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source

Symptomatic infection (Mild)

(Severe)

0.007 (0.005-0.01)

0.125 (0.104-0.152)

Infectious disease, acute episode, mild

Infectious disease, acute episode, severe

0.038

0.038

Stouthard, 1997

Stouthard, 1997

Latency period (before chronic Q fever)

 

 

0.5 (0.08-1.5)

Fenollar, 2001

Chronic Q fever

0.173 (0.14-0.205)

Heart failure, severe

1-1.5

CDC, 2013

References

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Dijkstra F, van der Hoek W, Wijers N, Schimmer B, Rietveld A, Wijkmans CJ, et al. The 2007–2010 Q fever epidemic in the Netherlands: Characteristics of notified acute Q fever patients and the association with dairy goat farming. FEMS Immunology and Medical Microbiology. 2012;64(1):3-12 (epub 2011/11/10).

ECDC Technical Report – Risk Assessment on Q fever. May 2010. Available at: http://www.ecdc.europa.eu/en/publications/Publications/1005_TER_Risk_Assessment_Qfever.pdf

Fenollar F, Fournier PE, Carrieri MP, Habib G, Messana T, Raoult D. Risks factors and prevention of Q fever endocarditis. Clinical Infectious Diseases, 2001 Aug 1;33(3):312-6.

Forland F, De Carvalho Gomes H, Nokleby H, Escriva A, Coulombier D, Giesecke J, et al. Applicability of evidence-based practice in public health: risk assessment on Q fever under an ongoing outbreak. Euro Surveill. 2012;17(3):pii=20060. Available at: http://www.eurosurveillance.org/ViewArticle.aspx?ArticleId=20060

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Q Fever Fact Sheet: Symptoms, Diagnosis, and Treatment – CDC, Atlanta. 2013. Available at: http://www.cdc.gov/qfever/symptoms/

Raoult D, Marrie T, Mege J. Natural history and pathophysiology of Q fever. Lancet Infectious Diseases, 2005 Apr;5(4):219-26.

Stouthard ME, Essink-Bot ML, Bonsel GJ, Barendregt JJ, Kramers PGN, van de Water HPA, et al. Disability Weights for Diseases in the Netherlands. Rotterdam, the Netherlands: Department of Public Health, Erasmus University Rotterdam, the Netherlands; 1997.

van der Hoek W, Meekelenkamp JC, Leenders AC, Wijers N, Notermans DW, Hukkelhoven CW. Antibodies against Coxiella burnetii and pregnancy outcome during the 2007-2008 Q fever outbreaks in The Netherlands. BMC Infectious Diseases, 2011 Feb 11;11:44.