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 10–20% of infected cases (Montoya, 2000). It is estimated that 4.67% (0–15.3%) of symptomatic cases will manifest more severe symptoms and approximately 2% (0–4.67%) 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 (1.5–1.7% 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 11–25%.

Asymptomatic congenital toxoplasmosis-infected infants have a 2% (1–3%) per year risk of developing chorioretinitis at a later age. The studies followed cases of asymptomatic congenital toxoplasmosis for 10–14 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% (12–15%) will develop permanent disabilities due to complications related to chorioretinitis, 11% (8–12%) to intracranial calcification, 3% (1-6%) to the central nervous system and 2% (1–3%) to hydrocephalus.

Model input summary

Table 1. Percentages used in the outcome tree

 Health outcome
 (Health state)

Distribution of health states in health outcome

Transition probability

Source/assumption

Acquired toxoplasmosis

 

 

 

Symptomatic infections:

(Uncomplicated)

(Complicated)

 

Remaining cases

4.67% (0–15.3%)

10–20%

 

Kemmeren, 2006

Chorioretinitis following symptomatic infection

 

2% (0–4.67%)

Kemmeren, 2006

Congenital toxoplasmosis

 

 

 

Symptomatic infections:

(Asymptomatic)

(Symptomatic)


75–89%

Remaining cases

 

Berrebi, 2010
Lebech, 1999
Schmidt, 2006

Permanent disability due to chorioretinitis after the first year following asymptomatic infection

 

2% (1-3%) per year (ATP) for 10–14 years

Havelaar, 2007
Starting one year after infection up to the age of 10–14 years

ATP: Annual Transition Probability

Permanent disability due to chorioretinitis within first year

 

13% (12–15%)

Havelaar, 2007

Permanent disability due to intracranial calcification

 

11% (8–12%)

Havelaar, 2007

Permanent disability due to hydrocephalus

 

2% (1–3%)

Havelaar, 2007

Permanent disability due to CNS abnormalities

 

3% (1–6%)

Havelaar, 2007

Fatal cases

 

0.7% (0.4–1.2%)

Havelaar, 2007

Table 2. Disability weights and duration

Health outcome
(Health state)

Disability Weight (DW) (Haagsma, 2015)

Duration

DW

Label

In years

Source

Acquired toxoplasmosis

 

 

 

 

Acquired toxoplasmosis

(Uncomplicated)

 

(Complicated)

 

0.007 (0.005–0.01)

0.125 (0.104–0.152)

 

Infectious disease, acute episode, mild

Infectious disease, acute episode, severe

0.04

Kemmeren, 2006

Congenital toxoplasmosis

 

 

 

 

Congenital toxoplasmosis
(Asymptomatic)

(Symptomatic)

 

0

0.125 (0.104–0.152)

 

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 (0.011–0.019)

Conjunctivitis without corneal scar

rem life exp.

Havelaar, 2007

Permanent disability due to chorioretinitis following symptomatic infections

0.015 (0.011–0.019)

Conjunctivitis without corneal scar

rem life exp.

Havelaar, 2007

Permanent disability due to intracranial calcification

0.044–0.087

Intellectual disability/mental retardation, from mild to moderate

rem life exp.

Havelaar, 2007

Permanent disability due to hydrocephalus

0.044–0.188

Intellectual disability/mental retardation, from mild to severe

rem life exp.

Havelaar, 2007

Permanent disability due to CNS abnormalities

0.056–0.407

Motor plus cognitive impairments, from mild to severe

rem life exp.

Havelaar, 2007

Permanent disability due to chorioretinitis

0.015 (0.011–0.019)

Conjunctivitis without corneal scar

rem life exp.

Kemmeren, 2006

References

Anand R, Jones CW, Ricks JH, Sofarelli TA, Hale DC. Acute primary toxoplasmosis in travelers returning from endemic countries. J Travel Med. 2012; 19(1): 57-60.

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.

Burnett AJ, Shortt SG, Isaac-Renton J, King A, Werker D, Bowie WR. Multiple cases of acquired toxoplasmosis retinitis presenting in an outbreak. Ophthalmology. 1998; 105(6): 1032-7.

Haagsma JA, Maertens de Noordhout C, Polinder S, Vos T, Havelaar AH, Cassini A, Devleesschauwer B, Kretzschmar ME, Speybroeck N, Salomon JA. Assessing disability weights based on the responses of 30,660 people from four European countries. Population Health Metrics 2015; 13: 10

Havelaar AH, Kemmeren JM, Kortbeek LM. Disease burden of congenital toxoplasmosis. Clin Infect Dis. 2007; 44(11): 1467-74.

Henriquez SA, Brett R, Alexander J, Pratt J, Roberts CW. Neuropsychiatric disease and Toxoplasma gondii infection. Neuroimmunomodulation. 2009; 16(2): 122-33.

Kemmeren JM, Mangen, MJJ, van Duynhoven YTHP, Havelaar AH. Priority setting of foodborne pathogens: disease burden and costs of selected enteric pathogens. Bilthoven: National Institute of Public Health and Environment; 2006. Report No.: RIVM rapport 330080001.

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.

Rorman E, Zamir CS, Rilkis I, Ben-David H. Congenital toxoplasmosis--prenatal aspects of Toxoplasma gondii infection. Reprod Toxicol. 2006; 21(4): 458-72.

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.

Torrey EF, Yolken RH. Toxoplasma gondii and schizophrenia. Emerg Infect Dis. 2003; 9(11): 1375-80.