Toxoplasmosis
Acquired toxoplasmosis
In Europe, most cases of acquired toxoplasmosis are asymptomatic and self-limiting (Rorman, 2006). Acquired toxoplasmosis will lead to symptomatic illness in approximately 1020% of infected cases (Montoya, 2000). It is estimated that 4.67% (015.3%) of symptomatic cases will manifest more severe symptoms and approximately 2% (04.67%) are at risk of developing life-long sequelae relative to chorioretinitis. However, it is unclear if this risk is attributable mainly to more severe, symptomatic infections or all infections (Kemmeren, 2006). All other symptomatic cases will manifest minor symptoms, such as fever and lymphoadenopathy (Rorman, 2006; Anand, 2012).
Mortality due to acquired toxoplasmosis is extremely rare and occurs in immunocompromised patients. It has therefore been decided to exclude fatal cases from the outcome tree of acquired toxoplasmosis.
Toxoplasmosis may also play a role in the development of psychiatric disorders, such as schizophrenia and bipolar depression (Torrey, 2003; Henriquez, 2009; Brown, 2010). However, insight into causality is still insufficient and these sequelae are not included in the model.
Congenital toxoplasmosis
Vertical transmission from a recently infected pregnant woman to her foetus may lead to congenital toxoplasmosis. Infections occurring during the first and second trimester of pregnancy may result in foetal loss (1.51.7% of seroconverting pregnant women, Havelaar 2007) or stillbirth (although neither of these are included in the present burden estimation) and symptoms in newborn infants are generally more severe. However, if the infection occurs in the third trimester the disease manifestation is generally subclinical. When present, symptoms vary from a triad including chorioretinitis, intracranial calcification and hydrocephalus to abnormalities of the central nervous system. These complications may lead to life-long sequelae, including subclinical congenital toxoplasmosis which could increase the risk of developing chorioretinitis later in life. Death can occur in a small proportion of infections. Other symptoms are very rare and have not been considered in this model.
Several studies have described clinical manifestations and follow-up of newborns infected with toxoplasmosis: 89% of children were asymptomatic at birth (16% of them developed chorioretinitis later in life) (Berrebi, 2010), 85% had no clinical findings at birth (Lebech, 1999) and 74.5% were asymptomatic at birth (Schmidt, 2006). Therefore, the proportion of asymptomatic infections out of the total congenital toxoplasmosis infections is 1125%.
Asymptomatic congenital toxoplasmosis-infected infants have a 2% (13%) per year risk of developing chorioretinitis at a later age. The studies followed cases of asymptomatic congenital toxoplasmosis for 1014 years (Havelaar, 2007).
Based on an extensive literature review, Havelaar et al. (Haavelar, 2007) estimated the risk of developing permanent disabilities related to congenital toxoplasmosis infections. We applied the same estimates to our model for all infections: 13% (1215%) will develop permanent disabilities due to complications related to chorioretinitis, 11% (812%) to intracranial calcification, 3% (1-6%) to the central nervous system and 2% (13%) to hydrocephalus.
Model input summary
Table 1. Percentages used in the outcome tree
Health outcome |
Distribution of health states in health outcome |
Transition probability |
Source/assumption |
Acquired toxoplasmosis |
|
|
|
Symptomatic infections: (Uncomplicated) (Complicated) |
Remaining cases 4.67% (015.3%) |
1020%
|
Kemmeren, 2006 |
Chorioretinitis following symptomatic infection |
|
2% (04.67%) |
Kemmeren, 2006 |
Congenital toxoplasmosis |
|
|
|
Symptomatic infections: (Asymptomatic) (Symptomatic) |
Remaining cases |
|
Berrebi,
2010 |
Permanent disability due to chorioretinitis after the first year following asymptomatic infection |
|
2% (1-3%) per year (ATP) for 1014 years |
Havelaar,
2007 ATP: Annual Transition Probability |
Permanent disability due to chorioretinitis within first year |
|
13% (1215%) |
Havelaar, 2007 |
Permanent disability due to intracranial calcification |
|
11% (812%) |
Havelaar, 2007 |
Permanent disability due to hydrocephalus |
|
2% (13%) |
Havelaar, 2007 |
Permanent disability due to CNS abnormalities |
|
3% (16%) |
Havelaar, 2007 |
Fatal cases |
|
0.7% (0.41.2%) |
Havelaar, 2007 |
Table 2. Disability weights and duration
Health
outcome |
Disability Weight (DW) (Haagsma, 2015) |
Duration |
||
DW |
Label |
In years |
Source |
|
Acquired toxoplasmosis |
|
|
|
|
Acquired toxoplasmosis (Uncomplicated)
(Complicated) |
0.007 (0.0050.01) 0.125 (0.1040.152) |
Infectious disease, acute episode, mild Infectious disease, acute episode, severe |
0.04 |
Kemmeren, 2006 |
Congenital toxoplasmosis |
|
|
|
|
Congenital toxoplasmosis (Symptomatic) |
0 0.125 (0.1040.152) |
Infectious disease, acute episode, mild Infectious disease, acute episode, severe |
1
0.167 |
Assuming chorioretinitis starts after one year Melse, 2000 |
Permanent disability due to chorioretinitis following asymptomatic infections |
0.015 (0.0110.019) |
Conjunctivitis without corneal scar |
rem life exp. |
Havelaar, 2007 |
Permanent disability due to chorioretinitis following symptomatic infections |
0.015 (0.0110.019) |
Conjunctivitis without corneal scar |
rem life exp. |
Havelaar, 2007 |
Permanent disability due to intracranial calcification |
0.0440.087 |
Intellectual disability/mental retardation, from mild to moderate |
rem life exp. |
Havelaar, 2007 |
Permanent disability due to hydrocephalus |
0.0440.188 |
Intellectual disability/mental retardation, from mild to severe |
rem life exp. |
Havelaar, 2007 |
Permanent disability due to CNS abnormalities |
0.0560.407 |
Motor plus cognitive impairments, from mild to severe |
rem life exp. |
Havelaar, 2007 |
Permanent disability due to chorioretinitis |
0.015 (0.0110.019) |
Conjunctivitis without corneal scar |
rem life exp. |
Kemmeren, 2006 |
References
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Berrebi A, Assouline C, Bessieres MH, Lathiere M, Cassaing S, Minville V, et al. Long-term outcome of children with congenital toxoplasmosis. American journal of obstetrics and gynecology. 2010; 203(6): 552 e1-6.
Brown AS, Derkits EJ. Prenatal infection and schizophrenia: a review of epidemiologic and translational studies. Am J Psychiatry. 2010; 167(3): 261-80.
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Lebech M, Andersen O, Christensen NC, Hertel J, Nielsen HE, Peitersen B, et al. Feasibility of neonatal screening for toxoplasma infection in the absence of prenatal treatment. Danish Congenital Toxoplasmosis Study Group. Lancet. 1999; 353(9167): 1834-7.
Melse JM, Essink-Bot ML, Kramers PG, Hoeymans N. A national burden of disease calculation: Dutch disability-adjusted life-years. Dutch Burden of Disease Group. Am J Public Health. 2000; 90(8): 1241-7.
Montoya J, Remingtons J. Toxoplasma gondii. In: Mandell G, Douglas, Benett J, editors. Principles and Practice of Infectious Diseases. Philadelphia: Churchill Livingstone; 2000.
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Schmidt DR, Hogh B, Andersen O, Fuchs J, Fledelius H, Petersen E. The national neonatal screening programme for congenital toxoplasmosis in Denmark: results from the initial four years, 1999-2002. Archives of disease in childhood. 2006; 91(8): 661-5.
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