Infections in Pregnancy Max Brinsmead PhD FRANZCOG

Syphilis A sexually transmitted infection caused by the spirochaetal bacterium Treponema pallidum A sexually transmitted infection caused by the spirochaetal bacterium Treponema pallidum Recognised in 3 stages in adults… Recognised in 3 stages in adults… Primary = a painless genital ulcer with lymphadenopathy. May go unrecognised Primary = a painless genital ulcer with lymphadenopathy. May go unrecognised Secondary = Fever, rash, anorexia, aches & pains. Occurs 2 – 8 weeks in only 1:3 individuals after primary infection and resolves spontaneously Secondary = Fever, rash, anorexia, aches & pains. Occurs 2 – 8 weeks in only 1:3 individuals after primary infection and resolves spontaneously Tertiary = can affect any body organ including heart, bones and brain Tertiary = can affect any body organ including heart, bones and brain

Diagnosis of Syphilis Diagnosed by a serological test for reagin – a lipid released from cells that are attacked by T. pallidum Diagnosed by a serological test for reagin – a lipid released from cells that are attacked by T. pallidum This test is sensitive and should revert to negative after treatment but… This test is sensitive and should revert to negative after treatment but… It is not positive until up to 12w after infection It is not positive until up to 12w after infection It is non-specific and there is a large number of conditions that cause a false positive test It is non-specific and there is a large number of conditions that cause a false positive test Tests that detect antibodies to Treponema are more specific but… Tests that detect antibodies to Treponema are more specific but… They are present for life even after successful treatment They are present for life even after successful treatment Yaws (and Pinta) will also be positive to these tests Yaws (and Pinta) will also be positive to these tests

Syphilis in Pregnancy Typically does not cross the placenta until >20 weeks Typically does not cross the placenta until >20 weeks Fetal effects include… Fetal effects include… Stillbirth Stillbirth Intrauterine growth restriction Intrauterine growth restriction Prematurity Prematurity Neonatal effects include… Neonatal effects include… Hepatosplenomegaly Hepatosplenomegaly Pneumonia Pneumonia Anaemia & Jaundice Anaemia & Jaundice Skin lesions Skin lesions Osteochondritis Osteochondritis

Treatment of Syphilis In the mother with a positive STS = serological test for syphilis In the mother with a positive STS = serological test for syphilis Give 3 doses of Benzathine penicillin 2.4 mU weekly Give 3 doses of Benzathine penicillin 2.4 mU weekly Erythromycin 500 mg 4 x daily for 15 – 30 days for true penicillin allergy Erythromycin 500 mg 4 x daily for 15 – 30 days for true penicillin allergy For a neonate For a neonate 25,000 IU/Kg Penicillin twice daily for 10 days 25,000 IU/Kg Penicillin twice daily for 10 days Follow up and treat the sexual partner Follow up and treat the sexual partner

Rubella in Pregnancy Max Brinsmead PhD FRANZCOG October 2008

Rubella Infection Caused by the pleomorphic RNA virus of the genus Rubivirus Caused by the pleomorphic RNA virus of the genus Rubivirus Infects only human subjects Infects only human subjects In adults and children causes: In adults and children causes: Mild fever & malaise Mild fever & malaise Generalised fine erythematous rash – rarely purpuric Generalised fine erythematous rash – rarely purpuric Cervical lymphadenopathy Cervical lymphadenopathy Arthralgia Arthralgia

Rubella in a Pregnant Woman Before 12 weeks pregnancy Before 12 weeks pregnancy Miscarriage Miscarriage Cardiac anomalies Cardiac anomalies Nerve deafness Nerve deafness Cataracts or retinopathy Cataracts or retinopathy Mental retardation Mental retardation Fetus somewhat safer in the 2 nd trimester but… Fetus somewhat safer in the 2 nd trimester but… In the second half of pregnancy In the second half of pregnancy Hepatosplenomegaly Hepatosplenomegaly Failure to thrive, osteitis Failure to thrive, osteitis Diabetes, hypothyroidism and GH deficiency Diabetes, hypothyroidism and GH deficiency Progressive panencephalitis Progressive panencephalitis = The Congenital Rubella Syndrome

Prevention of Congenital Rubella Immunise all children at m (MMR) Immunise all children at m (MMR) Test all women who are pregnant (or plan to conceive) for immunity Test all women who are pregnant (or plan to conceive) for immunity Avoid infection if pregnant Avoid infection if pregnant Spread by nasopharyngeal droplets +/- 7 days from the time of rash Spread by nasopharyngeal droplets +/- 7 days from the time of rash Retest any pregnant woman who is exposed to the virus Retest any pregnant woman who is exposed to the virus Terminate pregnancy for proven infection Terminate pregnancy for proven infection Immunise women postpartum if low titre or non immune Immunise women postpartum if low titre or non immune Immunisation of a pregnant woman with the live virus is not recommended but is also not associated with teratogenesis Immunisation of a pregnant woman with the live virus is not recommended but is also not associated with teratogenesis

Herpes in Pregnancy Max Brinsmead PhD FRANZCOG March 2010

Genital Herpes 66% caused by H. simplex Type 2 66% caused by H. simplex Type 2 33% associated with H simplex Type 1 33% associated with H simplex Type 1 Is a latent and recurrent infection in up to 1:5 adults Is a latent and recurrent infection in up to 1:5 adults ~1:50 women have this virus during pregnancy ~1:50 women have this virus during pregnancy But most are secondary (or recurrent) infections But most are secondary (or recurrent) infections Even if the woman says she has never had it before Even if the woman says she has never had it before

Maternal Herpes Primary infection can be disseminated with encephalitis, hepatitis and skin eruptions Primary infection can be disseminated with encephalitis, hepatitis and skin eruptions Is more common in pregnancy because of the mild immunosupression which occurs Is more common in pregnancy because of the mild immunosupression which occurs Concomitant HIV infection a real problem Concomitant HIV infection a real problem Most infections during pregnancy are secondary Most infections during pregnancy are secondary But recurrences are more common because of pregnancy-related immunosupression But recurrences are more common because of pregnancy-related immunosupression

Vertical Transmission of Herpes Mostly occurs when the fetus contacts infected genital secretions Mostly occurs when the fetus contacts infected genital secretions But intrauterine infection and FDIU possible But intrauterine infection and FDIU possible Neonatal infection is also possible Neonatal infection is also possible Disseminated Herpes occurs after primary maternal infection Disseminated Herpes occurs after primary maternal infection Often with premature delivery Often with premature delivery

Risk of Vertical Transmission With maternal primary Herpes the risk of neonatal infection is 26 – 56% With maternal primary Herpes the risk of neonatal infection is 26 – 56% With maternal secondary Herpes the risk of neonatal infection is 1 – 3% With maternal secondary Herpes the risk of neonatal infection is 1 – 3%

Diagnosis of Genital Herpes Often unrecognised in its recurrent form Often unrecognised in its recurrent form Typically localised pruritis and pain Typically localised pruritis and pain Blister and ulceration Blister and ulceration PCR is a sensitive and specific test if appropriate material is collected PCR is a sensitive and specific test if appropriate material is collected Serum IgG and IgM can be useful in distinguishing primary and secondary infection Serum IgG and IgM can be useful in distinguishing primary and secondary infection Viral culture Viral culture

Herpes visible at the onset of labour If thought to be a secondary infection then CS is not mandatory If thought to be a secondary infection then CS is not mandatory Requires patient counselling and her choice should be respected Requires patient counselling and her choice should be respected If there are ruptured membranes then delivery should be expedited If there are ruptured membranes then delivery should be expedited Fetal trauma should be avoided Fetal trauma should be avoided The neonatal service should be alerted The neonatal service should be alerted

Chickenpox in Pregnancy Max Brinsmead PhD MRCOG December 2007

Varicella Caused by Herpes zoster Caused by Herpes zoster Different epidemiology in temperate and tropical climates Different epidemiology in temperate and tropical climates Causes Causes Chickenpox Chickenpox Shingles Shingles Fetal varicella syndrome (FVS) Fetal varicella syndrome (FVS) In pregnancy maternal risks of pneumonitis (10%) are greater than the fetal risks of FVS (2%) In pregnancy maternal risks of pneumonitis (10%) are greater than the fetal risks of FVS (2%)

Fetal Varicella Syndrome Greatest risk is maternal infection 13 – 20w Greatest risk is maternal infection 13 – 20w Mental retardation 50% Mental retardation 50% Skin scarring Skin scarring Eye defects (micropthalmia, chorioretinitis and cataracts) Eye defects (micropthalmia, chorioretinitis and cataracts) Limb hypoplasia Limb hypoplasia Bowel/Bladder dysfunction Bowel/Bladder dysfunction

Neonatal Varicella Risk is greatest if maternal rash occurs 5 days before delivery and up to 2 days after Risk is greatest if maternal rash occurs 5 days before delivery and up to 2 days after Transmission rate 20 – 60% Transmission rate 20 – 60% 30% neonatal mortality if untreated 30% neonatal mortality if untreated Responds to the antiviral Acyclovir Responds to the antiviral Acyclovir

Maternal Varicella in Pregnancy Pneumonitis 10% Pneumonitis 10% Hepatitis Hepatitis Encephalitis Encephalitis Acyclovir recommended Acyclovir recommended

My Recommendations* Prenatal screening and/or Immunisation Prenatal screening and/or Immunisation ZIG for non immune women who come into close contact with Varicella ZIG for non immune women who come into close contact with Varicella Prophylactic oral Acyclovir for exposure >20w Prophylactic oral Acyclovir for exposure >20w Delay delivery >5 days after rash Delay delivery >5 days after rash Neonatal ZIG and Acyclovir for high risk neonate Neonatal ZIG and Acyclovir for high risk neonate Immunise health care workers Immunise health care workers Exclude those non immune to Varicella from care of pregnant women for 8 – 21days after possible infection Exclude those non immune to Varicella from care of pregnant women for 8 – 21days after possible infection

Cytomegalovirus Infection and Pregnancy Max Brinsmead PhD FRANZCOG December 2010

Cytomegalovirus Proper name is Human Herpesvirus 5 Proper name is Human Herpesvirus 5 1:100 babies are born with this congenital infection 1:100 babies are born with this congenital infection 1:10 of those infected will show some effect 1:10 of those infected will show some effect 1:10 of those will have severe mental retardation 1:10 of those will have severe mental retardation CMV is a common cause of mental retardation CMV is a common cause of mental retardation And causes 30% of congenital neural deafness And causes 30% of congenital neural deafness ~40% of women are non immune when pregnant ~40% of women are non immune when pregnant Health workers and women with children who bring home CMV are most at risk Health workers and women with children who bring home CMV are most at risk Vaccination is not possible Vaccination is not possible But trials are currently in progress But trials are currently in progress

Neonatal CMV Syndrome Small for dates Small for dates Failure to thrive Failure to thrive Hepatospenomegaly Hepatospenomegaly Microcephaly Microcephaly Cerebral calcifications Cerebral calcifications Chorioretinitis Chorioretinitis Hearing deficits (may occur later in life) Hearing deficits (may occur later in life) The virus can be detected in urine and saliva The virus can be detected in urine and saliva

Toxoplasmosis and Pregnancy Max Brinsmead PhD FRANZCOG October 2008

Toxoplasmosis Caused by the protozoan parasite Toxoplasma gondi Caused by the protozoan parasite Toxoplasma gondi Is endemic in most societies Is endemic in most societies And the definitive host is cats And the definitive host is cats Has a complex life cycle but infectious oocysts can live for many months in soil Has a complex life cycle but infectious oocysts can live for many months in soil 10 – 25% of adults have serologic evidence of previous infection 10 – 25% of adults have serologic evidence of previous infection In most it causes a mild illness with fever, malaise and lymphadenopathy In most it causes a mild illness with fever, malaise and lymphadenopathy But transplacental infection can cause congenital disease But transplacental infection can cause congenital disease

Congenital Toxoplasmosis Mental retardation Mental retardation Learning difficulties Learning difficulties Cerebral calcifications Cerebral calcifications Chorioretinitis  blindness Chorioretinitis  blindness Hydrocephalus Hydrocephalus Epilepsy Epilepsy

Vertical Transmission 50% of congenital Toxoplasmosis is due to eating contaminated meat, mostly pork 50% of congenital Toxoplasmosis is due to eating contaminated meat, mostly pork Remainder to to contact with cats’ faeces or contaminated soil Remainder to to contact with cats’ faeces or contaminated soil ~1:200 women will become infected during pregnancy ~1:200 women will become infected during pregnancy Of these ~1:10 will deliver a baby with congenital Toxoplamosis Of these ~1:10 will deliver a baby with congenital Toxoplamosis Infection in early pregnancy is less likely to cross the placenta Infection in early pregnancy is less likely to cross the placenta But this has more serious effects when it does But this has more serious effects when it does

Preventing Congenital Toxoplasmosis Pregnant women should: Cook meat thoroughly and check core temperature with a cooking thermometer Cook meat thoroughly and check core temperature with a cooking thermometer Prevent contamination of food by uncooked meat Prevent contamination of food by uncooked meat Avoid contact with cat faeces Avoid contact with cat faeces Wash or peel vegetables and avoid contact with soil Wash or peel vegetables and avoid contact with soil

Parvovirus Infection and Pregnancy Max Brinsmead PhD FRANZCOG December 2010

Parvovirus Caused by Parvovirus B19 Caused by Parvovirus B19 Causes epidemic Fifth Disease or “Slapped Cheek Syndrome” in pre school children. Causes epidemic Fifth Disease or “Slapped Cheek Syndrome” in pre school children. When intrauterine infection occurs it affects haemopoeisis. This results in fetal anaemia and hydrops fetalis. When intrauterine infection occurs it affects haemopoeisis. This results in fetal anaemia and hydrops fetalis. However, recovery is usually spontaneous and complete and there are no long term sequelae However, recovery is usually spontaneous and complete and there are no long term sequelae

Vertical Parvovirus Transmission 50-66% of pregnant women are Parvovirus immune 50-66% of pregnant women are Parvovirus immune Most infections occur from the mother’s own pre school child Most infections occur from the mother’s own pre school child Spread by droplets c sneezing, coughing Spread by droplets c sneezing, coughing Incubation period is days Incubation period is days Rash occurs on the face but also on hands, wrists & knees Rash occurs on the face but also on hands, wrists & knees Maternal symptoms include polyarthalgia, fever and non specific rash Maternal symptoms include polyarthalgia, fever and non specific rash Risk of maternal infection is increased by immune supression and during epidemics Risk of maternal infection is increased by immune supression and during epidemics

Fetal Risk Transplacental transmission rate is ~30% Transplacental transmission rate is ~30% Can cause hepatitis and myocarditis Can cause hepatitis and myocarditis 20% risk of fetal death in the 1 st trimester 20% risk of fetal death in the 1 st trimester Causes up to 3% of miscarriages Causes up to 3% of miscarriages Risk of hydrops is greatest in the second trimester Risk of hydrops is greatest in the second trimester When a fetal death rate of about 15% When a fetal death rate of about 15% But by 20w the risk of fetal death has fallen to 6% But by 20w the risk of fetal death has fallen to 6%