Clinical Guideline: Toxoplasmosis in Pregnancy

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Policy

Clinical Guideline
Toxoplasmosis in pregnancy

Policy developed by: SA Maternal & Neonatal Clinical Network


Approved SA Health Safety & Quality Strategic Governance Committee on:
24 June 2015
Next review due: 24 June 2018

Summary Guideline for the management of the pregnant woman with


Toxoplasmosis

Keywords toxoplasmosis, parasite, tosoplasma gondii, seropositive, meat,


cats faeces, vegetables, fruits, standard precautions, congenital,
chorioretinitis, hydrocephalus, intracranial calcification, raw meat,
soil, igm, iga, igg, polymerase chain reaction, pcr, amniotic,
infection, ultrasound, amniocentesis, rovamycine, spiramycin,
atovaquone, azithromycin, ophthalmological, parasites, autopsy,
ultrasound, cerebrospinal fluid, chorioretinitis, retinal scarring,
intracranial calfication, hydrosephalus, hepatosplenomegaly,
pheumonia, thrombocytopenia, lymphadenopathy, myocarditis,
neonate, Toxoplasmosis in pregnancy clinical guideline

Policy history Is this a new policy? N


Does this policy amend or update an existing policy? Y v3.0
Does this policy replace an existing policy? Y
If so, which policies?

Applies to All Health Networks


CALHN, SALHN, NALHN, CHSALHN, WCHN, SAAS

Staff impact All Clinical, Medical, Nursing, Allied Health, Emergency, Dental,
Mental Health, Pathology

PDS reference CG126

Version control and change history

Version Date from Date to Amendment


1.0 03 Mar 04 21 Sept 10 Original version
2.0 21 Sept 10 20 May 13 Reviewed
3.0 20 May 13 24 Jun 15 Reviewed
4.0 24 Jun 15 Current
© Department for Health and Ageing, Government of South Australia. All rights reserved.
South Australian Perinatal Practice Guidelines

toxoplasmosis in
pregnancy
© Department of Health, Government of South Australia. All rights reserved.

Note

This guideline provides advice of a general nature. This statewide guideline has been prepared to promote and facilitate
standardisation and consistency of practice, using a multidisciplinary approach. The guideline is based on a review of
published evidence and expert opinion.
Information in this statewide guideline is current at the time of publication.
SA Health does not accept responsibility for the quality or accuracy of material on websites linked from this site and does not
sponsor, approve or endorse materials on such links.
Health practitioners in the South Australian public health sector are expected to review specific details of each patient and
professionally assess the applicability of the relevant guideline to that clinical situation.
If for good clinical reasons, a decision is made to depart from the guideline, the responsible clinician must document in the
patient’s medical record, the decision made, by whom, and detailed reasons for the departure from the guideline.
This statewide guideline does not address all the elements of clinical practice and assumes that the individual clinicians are
responsible for discussing care with consumers in an environment that is culturally appropriate and which enables respectful
confidential discussion. This includes:
• The use of interpreter services where necessary,
• Advising consumers of their choice and ensuring informed consent is obtained,
• Providing care within scope of practice, meeting all legislative requirements and maintaining standards of
professional conduct, and
• Documenting all care in accordance with mandatory and local requirements
Explanation of the aboriginal artwork:
The aboriginal artwork used symbolises the connection to country and the circle shape shows the strong relationships amongst families and the aboriginal culture. The horse shoe shape
design shown prior to the generic statement symbolises a woman and those enclosing a smaller horse shoe shape depicts a pregnant women. The smaller horse shoe shape in this instance
represents the unborn child. The artwork shown before the specific statements within the document symbolises a footprint and demonstrates the need to move forward together in unison.

Australian Aboriginal Culture is the oldest living culture in the world yet we
experience the worst health outcomes in comparison. Our Aboriginal women are
2-5 times more likely to die in childbirth and our babies are 2-3 times more likely to
be low birth weight. Despite these unacceptable statistics the birth of an Aboriginal
baby is an important Cultural event and diverse protocols during the birthing
journey may apply.

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected] Page 1 of 8
South Australian Perinatal Practice Guidelines

toxoplasmosis in pregnancy

Toxoplasmosis
 Toxoplasmosis is caused by a parasite, Toxoplasma gondii. It is usually asymptomatic or
may have mild non-specific symptoms (e.g. malaise, fever, and lymphadenopathy)
 Toxoplasma remains latent for life, with clinical reactivation confined to severely
1
immunosuppressed individuals
 Infants of women who are seropositive before pregnancy are not at risk

Route of transmission
 Toxoplasmosis is acquired through
 Eating raw or undercooked meat

 Not washing hands thoroughly after handling raw meat or gardening, or


contact with cats faeces (directly or indirectly through the soil, or possibly
3
contaminated raw vegetables or fruits)
1
 Direct contact with cats is rarely a source of transmission

Infection precautions
 Standard precautions

Literature review
1
 In Australia, primary infection with toxoplasmosis during pregnancy is rare The risk of
maternal-fetal transmission and abnormalities related to congenital toxoplasmosis infection
is related to the gestation at maternal seroconversion

≤ 13 week’s gestation:
 5 - 15 % risk of maternal-fetal transmission
 60 - 80 % chance of abnormalities if infected

Second trimester:
 25 - 40 % risk of maternal-fetal transmission
 15 - 25 % chance of abnormalities if infected

Third trimester:
 30 - 75 % risk of maternal-fetal transmission

36 week’s gestation:
 72 % risk of maternal-fetal transmission
5,7
 2 - 10 % chance of abnormalities if infected
 Abnormalities following severe congenital toxoplasmosis are more common amongst babies
5,6
of women who seroconverted early in their pregnancy
 Abnormalities related to congenital toxoplasmosis are:
 Chorioretinitis

 Hydrocephalus

 Intracranial calcification

 Mental retardation

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected]
South Australian Perinatal Practice Guidelines

toxoplasmosis in pregnancy

Precautions to avoid maternal exposure to toxoplasmosis


Encourage all pregnant women to:
 Avoid raw / undercooked meat
 Avoid contamination of chopping boards, etc. with raw meat
 Wash hands after disposal of cat litter, gardening or handling raw meat
1
 Peel or wash raw fruit and vegetables thoroughly to remove contaminating soil (Gilbert
2002)

Maternal exposure
 Women who are pregnant in South Australia are not routinely screened for the presence of
IgG antibodies or toxoplasma-specific IgM antibodies
 Consider serology (IgG and IgM antibodies to toxoplasma gondii) for women who are
pregnant with symptoms of acute toxoplasmosis (e.g. malaise, fever, lymphadenopathy)

IgG and IgM negative


 Indicates no past infection
 Educate regarding precautions to avoid infection with toxoplasmosis
 Repeat if symptomatic

IgG positive IgM negative


 Indicates past infection

IgG and IgM positive


 Indicates possible recent infection
 IgM can remain positive for months or years; IgA, rising IgG level and / or low IgG avidity
are more specific for recent infection
 Repeat serology for IgM, IgA, and / or IgG titre and avidity
 A repeat high positive IgM, positive IgA and low IgG avidity is consistent with recent
toxoplasmosis

Maternal management
Following confirmation of recent maternal toxoplasmosis

Investigations
 Ultrasound to detect abnormalities
 Amniocentesis for polymerase chain reaction (PCR) and / or culture at 18 - 20 weeks
gestation or if ≥ 4 weeks after maternal infection
 PCR on amniotic fluid has a high sensitivity and specificity for the diagnosis of fetal
4
infection
 If the ultrasound and amniocentesis are negative, consider pharmacological treatment as
below if maternal infection is fairly certain

Note: A Cochrane Review has shown there have been no randomised trials of treatment for
2
toxoplasmosis in pregnancy . Treatment decisions should bear this in mind.
7
Management algorithms are available in Palasanthiran P, et al. and Montoya J G and
11
Remington JS.

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected]
South Australian Perinatal Practice Guidelines

toxoplasmosis in pregnancy

Infection in first 12 weeks gestation


 Administer spiramycin [Rovamycine®]. Not in stock in South Australia
 May be able to obtain supply from Monash Medical Centre Pharmacy or otherwise within a
week from overseas via LINK Pharmaceuticals Bridgepoint Mosman, NSW. 2088.
Telephone: (02) 9960 0150
 See Drug Interactions listed in Neonatal Management section
 Mild to moderate infections: 6,000,000 to 9,000,000 int. units (4 - 6 capsules of
spiramycin [Rovamycine®] "500" per day) in 2 divided doses

 Severe infections: 12,000,000 to 15,000,000 int. units (8 - 10 capsules of


spiramycin [Rovamycine®] "500" per day) in 2 divided doses
 Counsel woman / partner regarding termination if amniocentesis PCR positive

Infection from 13 to 27 weeks


 Administer spiramycin [Rovamycine®] (sulfadiazine and pyrimethamine are no longer
available)
 Mild to moderate infections: 6,000,000 to 9,000,000 int. units (4 - 6 capsules of
spiramycin [Rovamycine®] "500" per day) in 2 divided doses

 Severe infections: 12,000,000 to 15,000,000 int. units (8 - 10 capsules of


spiramycin [Rovamycine®] "500" per day) in 2 divided doses
 If there is delay in obtaining spiramycin, administer Atovaquone 750 mg twice daily (or
1,500 mg once daily if necessary) with food for 21 days
 Alternatively, Azithromycin 500 mg daily for 3 days repeated weekly for 4 weeks may be
tried. Its efficacy has not been proven but it has an IC50 of 1.2 mg / mL and concentrates in
2
tissues, especially the placenta
 Counsel woman / partner regarding termination if ultrasound abnormal

Infection from 28 to 42 weeks


®
 Administer spiramycin [Rovamycine ]
 Mild to moderate infections: 6,000,000 to 9,000,000 int. units (4 - 6 capsules of
spiramycin [Rovamycine®] "500" per day) in 2 divided doses
 Severe infections: 12,000,000 to 15,000,000 int. units (8 - 10 capsules of
spiramycin [Rovamycine®] "500" per day) in 2 divided doses
OR if unavailable:
 Administer Atovaquone 750 mg twice daily (or 1,500 mg once daily if necessary) with food
for 21 days
 Alternatively, Azithromycin 500 mg daily for 3 days repeated weekly for 4 weeks may be
tried

Intrapartum care
 Paediatrician at delivery
 Following delivery, newborn assessment should include physical examination for evidence
of congenital toxoplasmosis (including ophthalmological examination and cerebral
ultrasound)
 Placenta for histology / PCR
 May direct room-in with mother following initial assessment in nursery
 Use standard precautions (Parasites may be excreted in urine and other body fluids. A case
8
of toxoplasmosis acquired during performance of an autopsy has been described) (Neu
1967)

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected]
South Australian Perinatal Practice Guidelines

toxoplasmosis in pregnancy

Postnatal follow up
 Involvement of a specialist infectious diseases physician may be helpful

Neonatal management
Investigations
 Ophthalmological assessment and cerebral ultrasound
 Infant whole blood for PCR, and serology for toxoplasma-specific IgM and / or IgA,
persistent IgG
 Cerebrospinal fluid for PCR

Asymptomatic congenital toxoplasmosis


 The majority of infected babies will be asymptomatic
 Includes babies with positive serology and / or IgG that persists for more than 6 months

Symptomatic congenital toxoplasmosis


 A small minority of babies will have symptomatic congenital toxoplasmosis (IgM or PCR
positive with an IgG titre significantly greater than mothers) e.g:
 Chorioretinitis / retinal scarring

 Intracranial calcification

 Hydrocephalus

 Hepatosplenomegaly

 Pneumonia

 Thrombocytopenia

 Lymphadenopathy

 Myocarditis and IgM positive and / or abnormal placenta and / or cerebrospinal


fluid abnormality (PCR positive)

Drug treatment
 Administer spiramycin oral syrup: available in 75 000 units / mL (25 mg / mL)
 Neonate: Dosage by body weight; usual dosage 150,000 int. units / kg
(50 mg / kg) twice daily

Drug Interactions:
 Substrate of CYP3A4 (major)
 CYP3A4 inducers: CYP3A4 inducers may decrease the levels/effects of spiramycin.
Example inducers include aminoglutethimide, carbamazepine, nafcillin, nevirapine,
phenobarbital, phenytoin, and rifamycins
 CYP3A4 inhibitors: May increase the levels/effects of spiramycin. Example inhibitors include
azole antifungals, ciprofloxacin, clarithromycin, diclofenac, doxycycline, erythromycin,
imatinib, isoniazid, nefazodone, nicardipine, propofol, protease inhibitors, quinidine, and
verapamil
 Levodopa / carbidopa: Spiramycin has been reported to decrease carbidopa absorption and
decrease levodopa concentrations

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected]
South Australian Perinatal Practice Guidelines

toxoplasmosis in pregnancy

Follow up
 Continue above drug treatment for the first 12 months
 Repeat IgG at 6 months
 Regular paediatric / infectious diseases review is recommended

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected]
South Australian Perinatal Practice Guidelines

toxoplasmosis in pregnancy

References
1. Gilbert GL. Infections in pregnant women. MJA 2002; 176: 229-236.
2. Peyron F,WallonM, Liou C, Garner P. Treatments for toxoplasmosis in pregnancy.
Cochrane Database of Systematic Reviews 1999, Issue 3. Art. No.: CD001684. DOI:
10.1002/14651858.CD001684 (Level I). Available from URL:
http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD001684/pdf_fs.h
tml
3. Di Mario S, Basevi V, Gagliotti C, Spettoli D, Gori G, D’Amico R, Magrini N. Prenatal
education for congenital toxoplasmosis. Cochrane Database of Systematic Reviews
2009, Issue 1. Art. No.: CD006171. DOI:10.1002/14651858.CD006171.pub2.
Available from URL:
http://www.mrw.interscience.wiley.com/cochrane/clsysrev/articles/CD006171/pdf_fs.h
tml
4. Karunajeewa H, Siebert D, Hammond R, Garland S, Kelly H. Seroprevalence of
varicella zoster virus, parvovirus B19 and Toxoplasma gondii in a Melbourne obstetric
population: implications for management. ANZJOG 2001; 41: 23-28 (Level IV).
5. Dunn D, Wallon M, Peyron F, Petersen E, Peckham C, Gilbert R. Mother-to-child
transmission of toxoplasmosis: risk estimates for clinical counselling. The Lancet
1999; 353: 1829-33 (Level IV).
6. Langford KS. Infectious disease and pregnancy. Current Obstet Gynaecol 2002; 12:
125-30.
7. Palasanthiran P, Starr M, Jones C, Giles M, editors. Management of perinatal
infections. Sydney: Australasian Society for Infectious Diseases (ASID) 2014.
Available from: URL: http://www.asid.net.au/resources/clinical-guidelines
8. Neu HC. Toxoplasmosis transmitted at autopsy. JAMA 1967; 202:844-5 (Level IV).
9. Peyron F, Wallon M. Options for the pharmacotherapy of toxoplasmosis during
pregnancy. Expert Opinion in Pharmacotherapy. 2001; 2(8):1269-1274.
10. British National Formulary for Children (BNFC). Drugs for toxoplasmosis –
Spiramycin. London: The Royal Pharmaceutical Society of Great Britain; 2009.
11. Montoya J G and Remington JS. Management of Toxoplasma gondii Infection
during Pregnancy. Clin Infect Dis. 2008;47:554–66.

Useful web sites:


Organisation of teratology information specialists – Toxoplasmosis and pregnancy. Available
from URL:
http://www.otispregnancy.org/pdf/toxoplasmosis.pdf

South Australian Department of Health. You’ve got what – Toxoplasma infection. Available
from URL: www.sahealth.sa.gov.au/youvegotwhat in the A to Z index

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected]
South Australian Perinatal Practice Guidelines

toxoplasmosis in pregnancy

Abbreviations

e.g. For example


et al And others
IgG Immunoglobulin G
IgA Immunoglobulin A
IgM Immunoglobulin M
mg Milligram/s
mL Millilitre/s
PCR Polymerase chain reaction

Version control and change history


PDS reference: OCE use only

Version Date from Date to Amendment


1.0 03 Mar 04 21 Sept 10 Original version
2.0 21 Sept 10 20 May 13 Reviewed
3.0 20 May 13 24 Jun 15 Reviewed
4.0 24 Jun 15 Current

ISBN number: 978-1-74243-752-1


Endorsed by: South Australian Maternal & Neonatal Clinical Network
Last Revised: 30/06/15
Contact: South Australian Perinatal Practice Guidelines Workgroup at:
[email protected]

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