Viral infections in pregnancy: advice for healthcare workers.

Accepted Manuscript Viral infections in pregnancy: advice for healthcare workers T.L. Chin, A.P. MacGowan, S.K. Jacobson, M. Donati PII:

S0195-6701(14)00066-8

DOI:

10.1016/j.jhin.2013.12.011

Reference:

YJHIN 4316

To appear in:

Journal of Hospital Infection

Received Date: 16 June 2013 Accepted Date: 2 December 2013

Please cite this article as: Chin TL, MacGowan AP, Jacobson SK, Donati M, Viral infections in pregnancy: advice for healthcare workers, Journal of Hospital Infection (2014), doi: 10.1016/ j.jhin.2013.12.011. This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.

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Viral infections in pregnancy: advice for healthcare workers

a

Southmead Hospital, North Bristol NHS Trust, Bristol, UK

b

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T.L. China,*, A.P. MacGowana, S.K. Jacobsona, M. Donatib

*

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Public Health England, Bristol Public Health Laboratory, Department of Virology Bristol, UK

Corresponding author. Address: Microbiology Department, Royal United Hospital Bath NHS Trust, Combe Park,

Bath BA1 3NG, UK. Tel.: +44 (0)1225 825428; fax: +44 (0)1225 448262. E-mail address: [email protected] (T.L. Chin).

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SUMMARY Background: Healthcare workers (HCWs) have the potential for increased exposure to infectious

some infections for the mother and her unborn child.

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disease resulting from the provision of patient care. Pregnancy can confer specific problems in

Aims: To discuss the viral infections encountered in the UK that constitute a particular risk to the pregnant HCW: human immunodeficiency virus, hepatitis B virus, hepatitis C virus, varicella-

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zoster virus, herpes simplex virus, human parvovirus B19, cytomegalovirus, rubella, measles, enteroviruses, mumps and influenza. Evidence for nosocomial transmission, clinical aspects

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specific to pregnancy, and recommendations to protect the pregnant HCW at work are included. Methods: Medline, EMBASE and Pubmed were searched using a list of keywords specific to each viral infection, including ‘nosocomial’, ‘occupational’ and ‘healthcare workers’. References from the bibliographies of articles identified were reviewed for relevant material.

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Findings: The evidence for increased risk in the healthcare setting for many of these infections, outside of outbreaks, is weak, possibly because of the application of standard protective infection control measures or because risk of community exposure is greater. The pregnant HCW should be

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advised on protective behaviour in both settings. Potential interventions include vaccination and reducing the likelihood of exposure through universal precautions, infection control and

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redeployment.

Conclusion: Protection of the pregnant HCW is the responsibility of the individual, antenatal care provider and employer, and is made possible through awareness of the risks and potential interventions both before and after exposure. If exposure occurs or if the HCW develops an infective illness, urgent specialist advice is required.

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Keywords: Nosocomial Healthcare associated

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Healthcare worker Pregnant

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Occupational

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Introduction In the context of infectious diseases, healthcare workers (HCWs) accept the potential for increased pathogen exposure resulting from the provision of patient care. In recognition of this risk, all

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efforts must be made to protect patients and staff from hospital-acquired infections. Pregnancy can confer specific problems in some infections for both the mother and her unborn child.

This review will discuss the viral infections encountered in the UK that constitute a

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particular risk to the pregnant HCW, namely human immunodeficiency virus (HIV), hepatitis B virus (HBV), hepatitis C virus (HCV), varicella-zoster virus (VZV), herpes simplex virus (HSV),

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human parvovirus B19, cytomegalovirus (CMV), rubella, measles, enteroviruses, mumps and influenza. Evidence for nosocomial transmission, clinical aspects specific to pregnancy, and recommendations to protect the pregnant HCW at work will be included. The evidence for increased risk in the healthcare setting for many of these viral infections, outside of outbreaks, is

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weak or absent, possibly because of the application of standard protective infection control measures or because the risk of community exposure often outweighs any healthcare-associated risk. This review will serve to increase awareness of standard practices and the options for

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Methods

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management, whilst noting that expert advice should be sought in each case.

Medline, EMBASE and Pubmed were searched using a list of keywords specific to each viral infection, and including ‘nosocomial’, ‘occupational’ and ‘healthcare workers’. Additional references from the bibliographies of the articles identified were also reviewed for relevant material.

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Blood-borne viruses Human immunodeficiency virus Epidemiology

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HCWs in resource-poor countries have a higher risk of occupational exposure to blood-borne viruses due to a higher prevalence of blood-borne diseases and unsafe practices.1 In the UK, an estimated 96,000 people were living with HIV by the end of 2011. The overall prevalence was 1.5

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per 1000 population, with the highest rates reported among men who have sex with men (47 per 1000) and the black African community (37 per 1000).2 The prevalence of HIV in healthcare

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settings will vary according to the characteristics of the local population, but is likely to be higher than in the general population. Approximately 24% of people with HIV were unaware of their infection in 2011.2

Transmission

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HIV is transmitted as a result of contact with infected blood and body fluids. The average risk of HIV transmission after percutaneous exposure to HIV-infected blood in healthcare settings is approximately three per 1000 injuries.3 Increased risk is associated with percutaneous exposures

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involving a larger quantity of blood and if the patient’s viral load is high.3 Mucocutaneous

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exposure carries an infection risk estimated at less than one in 1000.3 Risk of transmission following a bite will depend on the severity of the incident, the patient’s oral hygiene and stage of the disease.4

In the UK, there have been five documented and 47 probable HIV transmissions in HCWs

following exposure to HIV-positive source patients since 1984. The last case of HIV seroconversion in an occupationally exposed HCW was reported in 1999.5

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Clinical aspects directly relevant to pregnancy Infection with HIV during pregnancy complicates antiretroviral treatment and risks mother to child transmission (MTCT) through exposure in utero, at delivery or through breast feeding. In the UK,

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the MTCT rate has been reduced from approximately 26% to less than 1% with interventions such as antiviral treatment for the mother and prophylaxis for the baby.6 A small proportion of HIVpositive women remain undiagnosed at delivery in the UK; therefore, an estimated 2% of all HIV-

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Healthcare worker protection

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exposed infants are infected vertically.6

Standard infection control precautions (SICPs), including use of gloves, aprons, protective face/eyewear, and correct sharps handling procedures, can prevent the majority of mucocutaneous

Post exposure care

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and percutaneous exposures to blood-borne pathogens.7,8

HCWs should be aware of local protocols for the management of potential blood-borne virus

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exposure. After immediate first aid, there should be prompt risk assessment regarding the need for antiretroviral post exposure prophylaxis (PEP). It is recommended that PEP should be given within

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one hour of exposure, but not more than 72 h after exposure.3 The protective efficacy of HIV PEP is estimated at approximately 80%. Occupationally acquired HIV infection has been described despite PEP.9 If PEP is commenced, testing for HIV status of the source individual should determine whether to continue prophylaxis for the recommended 28 days.10

Impact on employment of infection or exposure in pregnancy

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There is no need for HCWs to avoid performing exposure-prone procedures (EPPs) pending serological follow-up after occupational exposure to any of the blood-borne viruses.3 In the UK, HIV-infected HCWs are currently restricted from performing EPPs.11 Worldwide, four untreated

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infected HCWs (none in the UK) are reported to have transmitted HIV infection to patients; therefore, it has been proposed that HIV-infected HCWs should be permitted to perform EPPs if they are on effective antiretroviral therapy.11 Guidelines in the USA have proposed allowing

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unrestricted clinical practice for HIV-infected HCWs with low viral load.12 Australian guidelines prevent HCWs from performing EPPs if they are HIV antibody positive, even if virus levels

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become undetectable on antiretroviral therapy.13

Hepatitis B virus Epidemiology

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The UK has low endemicity for chronic hepatitis B, of the order of 0.3%.14 However, in areas of high endemicity, such as parts of south-east Asia and sub-Saharan Africa, the prevalence of HBsAg is 8–20%, and approximately 70–90% of the population become infected with HBV before

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40 years of age.15 Risk groups in England and Wales include injecting drug users, people who change sexual partners frequently, and individuals from or travelling in high-prevalence areas.16

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The prevalence of HBV in hospitalized patients will reflect the characteristics of the local population.

Transmission

HBV is transmitted through mucosal or percutaneous exposure. The average risk of infection following a percutaneous injury to a non-immune individual is approximately 30% when the

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source patient is HBeAg positive,17 and in almost all reported cases has occurred when the source viral load was >105 geq/mL.18 Risk of transmission following mucocutaneous exposure is unquantified. MTCT occurs perinatally in utero or mucocutaneously. Worldwide, 37% of cases of

Clinical aspects directly relevant to pregnancy

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hepatitis B among HCWs are estimated to result from occupational exposure.19

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Pregnant women with HBV mono-infection typically have a similar course as the non-pregnant population.20 In contrast, HIV/HBV co-infection is associated with higher morbidity and mortality

reported in acute HBV infection.21

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than either infection alone.20 An increased rate of miscarriage and premature labour has been

Vertical transmission occurs in 70–90% of pregnancies where the mother is HBeAg positive,22 and risk is reduced significantly if the mother is HBeAg negative.23 There is a 90% risk

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that an infected infant will become a chronic carrier, compared with a 5–10% risk following infection in adulthood.17 Maternofoetal transmission of HBV is also related to the level of viraemia. Women with HBV DNA >107 IU/mL should be considered for antiviral therapy from the

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32nd week of pregnancy.24 No studies have reported an increase in vertical transmission of HBV in HIV/HBV co-infected women, but HIV may increase serum HBV DNA levels so this is

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plausible.20

In the UK, routine antenatal screening for HBsAg identifies those newborns who require

prophylaxis with vaccine with or without hepatitis B immunoglobulin (HBIG),16 which can prevent persistent hepatitis B infection in approximately 90% of infants.25 With appropriate immunoprophylaxis, infants of chronic HBV carriers may be breast fed with no additional risk for

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HBV transmission.26 World Health Organization guidelines state that an HBV-infected mother may breast feed with no additional risk to her infant, even without immunization.27

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SICPs are crucial to prevent exposure. All HCWs should receive the inactivated hepatitis B vaccine, which is considered safe to give to pregnant or breastfeeding women.16,28 Postvaccination

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screening for anti-HBs is recommended for those at risk of occupational exposure to identify

routine booster dose after five years.16

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suboptimal or non-response.16 Responders with anti-HBs ≥100 mIU/mL should receive a single

Following exposure and immediate first aid, expert advice should be obtained urgently. HBV

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vaccine can prevent infection post exposure, and is given concurrently with HBIG in high-risk situations or in a known vaccine non-responder. Individually, both HBIG and hepatitis B vaccine have demonstrated efficacy post exposure, and evidence suggests that vaccination increases the

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efficacy of post exposure immunoprophylaxis compared with immunoglobulin alone.29,30 PEP is thought to be effective if administered up to seven days after needlestick exposures.31 Indications

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for vaccination and HBIG can be found in Immunisation against infectious disease.16 Pregnant women may receive HBIG safely.31 If infection has occurred at the time of immunization, severe illness and development of the carrier state may be prevented.16


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Restrictions on practice of EPPs apply to HCWs with positive HBeAg status and/or who have a viral load >103 geq/mL during or after treatment.32 If monitored regularly, HCWs who are HBeAg negative with a pretreatment viral load of 103–105 geq/mL are allowed to perform EPPs while

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taking continuous oral antiviral therapy if their viral load is maintained below 103 geq/mL.32 In contrast, Australian guidelines state that HCWs must not perform EPP whilst HBsAg positive

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unless HBV DNA is consistently undetectable.13

Hepatitis C virus

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Epidemiology

The UK is thought to be a low-prevalence area, with approximately 216,000 people chronically infected with hepatitis C. Injecting drug use is the most important risk factor for infection.33 In England, an estimated 0.4% of the adult population are chronically infected.33 Prevalence in the

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local population will vary according to ethnic representation; in 2011, 2.8% of people of South Asian origin tested anti-HCV positive, and between 2008 and 2011, 6% of people of Eastern European origin tested anti-HCV positive.33 Patients receiving health care in the UK are likely to

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Transmission

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have a higher prevalence of HCV infection than the general population.

HCV is transmitted as a result of contact with blood and body fluids that are positive for HCV RNA, with an estimated risk following percutaneous injury of approximately 1.8%.34 Deep injury, injury from a hollow-bore needle from a vein or artery, and high-source viral load are risk factors for HCV transmission.35 Occupational mucocutaneous transmission has been reported rarely.36

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The total number of healthcare-associated hepatitis C virus seroconversions in HCWs reported


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between 1997 and 2011 stands at 20.5

Pregnancy does not appear to have a deleterious effect on the course of HCV infection,37 although a favourable effect of pregnancy on liver cell necrosis has been demonstrated.38 There is no

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evidence to suggest an association between maternal infection and low birth weight, congenital abnormalities or obstetric complications.37 MTCT is thought to occur predominantly in utero or

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intra partum. MTCT is correlated with high maternal viral titre,39 and is very uncommon if the mother is HCV RNA negative.40 The risk of HCV vertical transmission is higher in infants born to mothers with HCV/HIV co-infection,41 and girls appear to be twice as likely to be infected as boys.42 There are no definitive studies on the safety of HCV antiviral therapy during pregnancy.

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Interferon is contra-indicated in pregnancy unless the potential benefit outweighs the risk,43 and ribavirin should be avoided in pregnancy because of teratogenicity in animal species.43 Findings are conflicting with respect to any protective effect of elective caesarean delivery;38,44 it is not

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presently recommended by the American Academy of Pediatrics.45 There appears to be no additional risk of HCV transmission through breast feeding,45 although HCV RNA has been

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detected in breast milk.45 Given diagnostic limitations, the transmission rate is approximately 5%,45,46 and 14%, on average, in cases of HCV/HIV co-infection.45 Approximately 20% of children vertically infected with HCV appear to clear the infection, 50% develop chronic asymptomatic infection, and 30% develop chronic active infection.47


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SICPs are crucial to prevent exposure.

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Following immediate first aid, employees should follow local protocols for the management of potential blood-borne virus exposure incidents. There is no vaccine or post exposure chemoprophylaxis to prevent seroconversion. Testing for HCV RNA at six weeks, HCV RNA and

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anti-HCV at 12 weeks, and anti-HCV at 24 weeks is essential as treatment of acute infection has a

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higher success rate.48


Restrictions on practice of EPPs will apply to HCWs who test positive for HCV RNA.49

Varicella-zoster virus Epidemiology

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Herpes viruses

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In the UK and other temperate climates without routine childhood vaccination, varicella is a common infection of childhood; at least 85% of those aged over 15 years are thought to be

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immune due to prior infection.50

Transmission

Transmission is by direct contact with vesicle fluid, inhalation of aerosols from vesicular fluid or respiratory secretions, or indirectly via fomites. Most often, VZV appears to be transmitted by the

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droplet route, usually during close contact. The infectious period is from 48 hours before onset of the rash until the vesicles have crusted over. VZV transmission is well recognized both between patients and from patients to HCWs.

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Airborne transmission has led to the recommendation of negative pressure isolation of patients hospitalized with varicella,51 but this is not common practice. Transmission of chickenpox to HCWs from a patient with zoster has also been reported, despite lesions being covered most of the

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time.52 This may be accounted for by the detection of VZV DNA in the saliva of patients with herpes zoster.53 Immunocompetent people with zoster appear to be less contagious than people

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with varicella, but immunocompromised patients with zoster have high infectivity; over a five-year period at a UK teaching hospital, zoster was a more common cause of nosocomial infection than varicella.54 This may reflect the fact that it is feasible to avoid exposure to a patient admitted with

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chickenpox, whereas patients with zoster often develop symptoms whilst hospitalized.54

Clinical aspects directly relevant to pregnancy Increased morbidity and mortality has been reported with VZV infection in pregnant compared

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with non-pregnant adults, but there may have been bias towards reporting of more severe cases.55 In the UK, the overall mortality rate in pregnancy is low, although it is higher in late gestation,55

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with 10–14% of pregnant women having evidence of pneumonia; an incidence comparable with the general adult population.56 Risks to the foetus are related to the timing of maternal infection. Infection within the first 20 weeks of gestation may result in the foetal varicella syndrome (FVS) of skeletal, central nervous system (CNS), ocular, gastrointestinal and genito-urinary abnormalities; skin scarring and high mortality with an absolute risk of approximately 2%.57 FVS associated with maternal varicella during the third trimester is rare.56 Infection in the second and

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third trimesters has been associated with a 1.2% risk of herpes zoster in infancy or early childhood.58 Maternal chickenpox developing one week before to one week after delivery may cause severe neonatal varicella, with significant mortality in the absence of prophylaxis and/or

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antiviral therapy.


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Before employment, occupational health assessment should target susceptible non-pregnant HCWs who have direct patient contact for the live-attenuated vaccine.59 For UK-born HCWs, a history of

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a typical rash illness is 97–99% predictive of the presence of serum varicella antibodies,60 and is assumed to indicate immunity. HCWs with an uncertain or negative history should be tested for VZV immunoglobulin G.59 The vaccine is contra-indicated during pregnancy, although a registry of outcomes for seronegative pregnant women exposed to the vaccine reported no evidence of an

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increase in congenital anomalies among 131 live births,61 so inadvertent vaccination should not be a reason to terminate the pregnancy.62 Non-pregnant women who are vaccinated should avoid becoming pregnant for three months following the last dose.63 For HCWs who develop a

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generalized rash in the month after vaccination, it is important to determine by molecular analysis of virus samples whether the rash is vaccine related or wild-type chickenpox.64 Avoidance of

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patient contact until all lesions have crusted is necessary as vaccine virus has been transmitted to susceptible contacts.59,64 Breastfeeding women may be vaccinated safely; the vaccine virus has not been detected in breast milk.65 Airborne and contact precautions should be applied in the care of potentially infective

patients.66 Pregnant HCWs of any gestation who have no history of chickenpox or shingles, and who have not received two doses of a varicella-containing vaccine should avoid contact.

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Post exposure care Pregnant HCWs who have no history of chickenpox or shingles, and who have not received two

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doses of a varicella-containing vaccine should report exposures immediately. If serology confirms susceptibility and the contact is significant, defined as being in the same room for over 15 minutes or face-to-face contact,64,67 varicella zoster immunoglobulin (VZIG) should be offered as soon as

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possible but within ten days of contact and before chickenpox has developed. As airborne transmission at a distance has been reported occasionally, consideration should be given to giving

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VZIG to all susceptible high-risk contacts.64 VZIG may reduce in-utero transmission for mothers exposed during the first 36 weeks of gestation by attenuating maternal disease.68 Approximately 50% of susceptible pregnant women given VZIG after household exposure to chickenpox still develop clinical varicella, although the disease is often attenuated, and a further 25% will be

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infected subclinically.69 A study of 97 pregnancies in which maternal varicella infection followed post exposure VZIG prophylaxis found that there were no cases of FVS or zoster in infancy.58 Severe maternal varicella and death despite VZIG prophylaxis has been reported, and FVS has

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been reported in the infant of a woman exposed at 11 weeks of gestation who developed clinical varicella despite VZIG.57 Varicella vaccine can prevent or attenuate chickenpox infection if given

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within three days of rash onset in the index case,70 but is contra-indicated in pregnancy. The UK Advisory Group on Chickenpox recommends that pregnant women with onset of

chickenpox at more than 20 weeks of gestation should be prescribed oral aciclovir, provided that presentation is within 24 hours of rash onset.71 Hospital referral will be necessary if signs of severe or disseminated infection present.67 Aciclovir treatment before 20 weeks of gestation carries a theoretical risk of teratogenesis,72 and the manufacturer advises use only when the potential benefit

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outweighs the risk (no formal controlled trials). A recent Danish study that assessed more than 800,000 pregnancies suggests that exposure to aciclovir or valaciclovir in the first trimester is not associated with an increased risk of major birth defects. 73 The Aciclovir in Pregnancy Registry of

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749 pregnancies of women exposed to systemic aciclovir during the first trimester found no increase in birth defects; however, the registry is too small to evaluate the risk of less common defects.74 Aciclovir should only be used during pregnancy when the benefits clearly outweigh the

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potential risks.74 It is not clear whether treatment with aciclovir can prevent in-utero foetal transmission of the virus. If there is a risk of FVS, the woman should be referred to a foetal

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medicine specialist for consideration of ultrasound scanning and amniotic fluid polymerase chain reaction.71 Measures to prevent neonatal varicella include avoiding elective delivery until five to seven days after the onset of the maternal rash to allow for the transplacental transfer of antibodies,71 and administration of VZIG71 and prophylactic aciclovir67 to the neonate. Neonatal

virologist.71

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infection should be treated with aciclovir following discussion with the neonatologist and

Mothers with chickenpox or shingles should be allowed to breast feed provided that there

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are no lesions close to the nipple.67 Aciclovir should be administered to a nursing mother with caution and after risk assessment.74 A fully-breast-fed infant is estimated to ingest approximately

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1% of the oral maternal dose.75

Impact on employment of infection or exposure in pregnancy Susceptible HCWs should be excluded from patient contact from eight days after exposure until the end of the incubation period at 21 days,76 or up to 28 days if VZIG prophylaxis has been given

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if he or she remains asymptomatic.77 HCWs with chickenpox should be excluded from work until the lesions are crusted over, and similar precautions are usually applied to HCWs with zoster.

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Herpes simplex virus Epidemiology

Large inter- and intracountry differences in the seroprevalence of HSV-1 and HSV-2 have been

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observed.78 In the UK, HSV-1 antibody prevalence increases with age and has found to be 54% in females aged 25–30 years.79 In the USA, 2% or more of susceptible women have been shown to

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acquire HSV infection during pregnancy,80 but only a very small proportion are likely to be occupationally acquired.

Transmission

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The pregnant HCW’s risk of exposure to HSV is predominantly through non-occupational activities, and is extremely low in the healthcare environment if SICPs are applied. In health care, transmission is through contact with patients’ primary or recurrent lesions or with virus-containing

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secretions such as saliva, vaginal secretions and amniotic fluid. Patients more likely to be secreting HSV are those requiring augmented care; who have severe malnutrition, eczema or burns; or are

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immunocompromised. The patient may be symptomatic or asymptomatic. Most commonly, a HCW’s minor abrasions make contact with infected lesions or body fluids, and herpetic whitlow develops at that site. HCWs may have accounted for manual transmission of HSV to three secondary cases in an intensive care nursery.81


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Although it occurs rarely, pregnant women, particularly if immunocompromised, are more likely to suffer disseminated herpes with multi-organ involvement and its associated mortality of approximately 75% if untreated.82 Factors influencing clinical outcome for the neonate include

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type of maternal infection (primary or recurrent), presence of transplacental neutralizing antibodies, duration of rupture of membranes, use of foetal scalp electrodes and mode of delivery.83 Outcomes for the pregnancy include spontaneous abortion, prematurity, congenital

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herpes and neonatal herpes. Congenital herpes manifests as skin, eye and CNS involvement; intrauterine growth restriction or foetal death.83 Neonatal herpes infection usually occurs at delivery,

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but can occur in utero or postnatally. Between 1986 and 1991, 76 cases of neonatal HSV infection were reported to the British Paediatric Association Surveillance Unit; an incidence of 1.65 per 100,000 live births. Twenty-five infants had HSV-1 infection, 24 infants had HSV-2 infection and the virus type was unknown in 27 infants.84 Twenty-five percent of infants died in the neonatal

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period and a further 33% subsequently died or had long-term sequelae.84 Disease may be disseminated or localized to skin, eye, mouth or CNS. Disseminated herpes occurs almost exclusively as a result of primary maternal infection and is more common in preterm infants.

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Disseminated herpes carries a mortality of 70–85% mortality if untreated,82,85 and approximately 30% mortality and 17% neurological sequelae with antiviral therapy.83,85 Infants with skin, eye

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and/or mouth involvement rarely die, and morbidity is less than 2% with treatment.83,85 If treated, mortality with local CNS disease is 4–6% and neurological morbidity is 70%.83,85 Depending on the nature of maternal infection, prevention of neonatal HSV disease may involve treating the mother with aciclovir and/or caesarean delivery, neonatal assessment and prophylaxis.86


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Pregnant HCWs should be educated on the risks associated with acquisition and recurrence of HSV infection, and advised to apply standard precautions.

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Post exposure care

Women who are past 20 weeks of gestation can receive aciclovir safely, but a risk–benefit analysis should be made prior to 20 weeks of gestation. Management of the pregnancy in cases of non-

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genital herpes is expectant. Breast feeding is only contra-indicated in the event of a herpetic lesion

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on the breast.


The HCW with non-genital HSV infection should observe infection control procedures, which may involve redeployment, wearing gloves or an occlusive dressing, and treatment with aciclovir.

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Exclusion from patient contact may be required when it is impractical to cover lesions, or for HCWs managing high-risk patients. There have been no reports that personnel with genital HSV

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infections have transmitted HSV to patients; work restrictions are not indicated.77

Cytomegalovirus

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Epidemiology

In the UK, approximately 40% of women are susceptible to CMV at the time of pregnancy;87 however, seroprevalence varies with geographical region, socio-economic status88 and ethnicity.89 In hospital and day-care centres, children, especially infants and toddlers, have been found to have the highest age-related excretion rates.90

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Transmission CMV is transmitted through body fluids, blood transfusions, organ transplant and in utero. Primary infection, re-infection and re-activation are associated with viral shedding, with the highest

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excretion rates in immunosuppressed adults, and affected infants and toddlers.91 Studies have appeared to demonstrate the hospital as a risk factor for CMV acquisition,92 but are frequently undermined by failure/inability to control for the ubiquitous nature of CMV and a lack of strain

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comparison.90 HCWs who work with children have been shown to be at no greater risk of CMV seroconversion than other young women in the community.91 Acquisition appears to require close

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contact with infected people.90


CMV infection is asymptomatic in 90% of immunocompetent individuals, including pregnant

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women. CMV is the most common congenital infection in the UK, affecting an estimated three per 1000 livebirths89 and the most common non-genetic cause of childhood hearing loss.93 There was an estimated annual average of 2133 infections affecting pregnant females in England and Wales

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between 1991 and 2002.94 Vertical transmission occurs in approximately 40% of primary maternal CMV infections,95 and there is approximately 1% risk following secondary infection (i.e. re-

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activation or infection with a new virus strain).96 Re-activation is almost always clinically unapparent. Infection at an early stage of pregnancy is a higher risk for adverse outcome compared with later infection. The classical congenital CMV syndrome (CMV inclusion disease) is characterized

by

encephalitis,

microcephaly,

hydrocephalus,

intracranial

calcifications,

sensorineural deafness, chorioretinitis, bone translucencies, intra-uterine growth retardation, hepatitis, anaemia, petechiae, hepatosplenomegaly and pneumonitis. Approximately 90% of

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congenital infections are initially asymptomatic, but 10–15% of these subsequently develop sensorineural hearing loss and neurodevelopmental delay, and 10% display clinical manifestations

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at birth. Maternal CMV has been described as a possible aetiology of intra-uterine foetal death.97

Post exposure care

If a perceived high-risk exposure occurs, the HCW must be involved in and understand the

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implications of testing for evidence of past infection or susceptibility against the background of potential re-infection and re-activation, incubation period, and limited options for management of

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maternal and foetal infection. As maternal infection is usually mild or asymptomatic, diagnosis of acute infection in a pregnant woman is unusual. Serology to distinguish between primary infection and re-infection/re-activation should be considered for women who develop an influenza-like or glandular-fever-like illness during pregnancy or following detection of sonographic findings

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suggestive of CMV infection.98 Prenatal diagnosis of foetal CMV should be based on amniocentesis and serial ultrasound.98 CMV immunoglobulin may have a role in the prevention/treatment of CMV infection.99 CMV screening in pregnant women is not recommended

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in the UK.87

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Avoidance of exposure is difficult as CMV is ubiquitous in certain healthcare environments and in the community, and most individuals shedding CMV are not identified. Deployment into perceived lower-risk areas is unlikely to be an effective protective measure. HCWs should be advised to assume that children under the age of three years have CMV in their urine and saliva, and practise hygienic precautions.100

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Most infections will be unrecognized. SICPs are the mainstay of protection.

Exanthema Human parvovirus B19

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Epidemiology

Human parvovirus B19 is a common infection of childhood. A seroprevalence survey in England

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and Wales has estimated the age-specific risk as highest in children aged seven to nine years.101 The average proportion of women of childbearing age susceptible to parvovirus B19 infection has been estimated at 38%.101 Annual seroconversion rates among pregnant Danish women during endemic and epidemic periods were found to be 1.5% and 13%, respectively.102 Epidemiological

Transmission

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differences are found within Europe101 and worldwide.

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During infection, parvovirus B19 DNA can be detected in respiratory secretions and serum. The virus is transmitted primarily through aerosol, droplets or fomites, but also through transfusion of

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blood or blood products, and vertical transmission. The typical incubation period for erythema infectiosum is 13–18 days; however, asymptomatic infection is common. Parvovirus is much less infectious than varicella, although the definition of significant contact used is the same.103 Development of the characteristic rash or polyarthropathy indicates the end of the infectious period.

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There is no clear excess risk of healthcare-associated transmission compared with the background community,103 with household exposure being most important. Hospitalized patients with aplastic crisis have been identified as a source of infection,104 but other studies prompted by

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recognized prolonged exposures to unisolated patients with transient aplastic crisis have reported a lack of transmission.105,106 This risk of healthcare-associated transmission is likely to be overestimated when gauged from outbreaks.105 Risk of transmission may be related to the level of

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viraemia in the index case106 and likelihood of exposure to respiratory secretions.

Infection in pregnancy results in a maternal illness clinically similar to that in non-pregnant adults. Symptomatic and asymptomatic infection can result in vertical transmission.107 Risk of intrauterine infection increases with gestational age.108 However, the greatest risk of adverse outcome is

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during the first 20 weeks of gestation, with a 9% excess risk of miscarriage109 including a 3% risk of foetal hydrops during gestational weeks nine to 20.109 Myocarditis, pleural and pericardial effusions, hepatitis, neurological defects and persistent neonatal anaemia have been described.110

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Associations with congenital malformations are unproven.111 The risk after 20 weeks of gestation is uncertain. Prior immunity does not prevent re-infection; however, re-infection is not a risk to the

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foetus.67

Healthcare worker protection Avoidance of exposure is difficult, and non-occupational exposure risk is probably greater than any work-related risk during epidemic years. SICPs to prevent contact with secretions and frequent handwashing are probably effective in reducing healthcare-associated transmission. Pregnant

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HCWs should not be assigned to care for patients with chronic B19 infection or transient aplastic crisis,112 who should be nursed in side rooms with respiratory isolation precautions.113 In the event of a confirmed workplace outbreak, the pregnant HCW should not be excluded routinely but it

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should be her personal decision, after susceptibility has been established and following discussions with family, physician and employer.103 At the time of recognizing a workplace outbreak, exposure

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may already have occurred and access to rapid testing to define susceptibility is useful.

Post exposure care

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Pregnant women who have significant contact with a non-vesicular rash illness should be evaluated simultaneously for susceptibility for rubella and parvovirus B19 infection, and a risk assessment should be undertaken for the likelihood of measles in the index patient.67 Pregnant women who develop a rash of suspected infectious cause should have investigations for recent

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parvovirus and rubella infection regardless of past rubella immunity. Tests for other infections such as measles, glandular fever and enterovirus will be determined by the clinical setting. In the UK, women who test positive for parvovirus B19 immunoglobulin M and/or DNA in the first 20

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weeks of gestation will require regular ultrasound scans; local obstetric practice on the management of infection after 20 weeks of gestation may vary. Findings suggestive of foetal

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hydrops should precipitate referral to the regional unit of foetal medicine for consideration of foetal blood sampling and intra-uterine transfusion.67 Parvovirus B19 antibody screening in pregnancy is not advised.114


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Usually, infected and immunocompetent HCWs do not require isolation or exclusion by the time of diagnosis. Further guidance is provided by Crowcroft et al.103 However, until serological confirmation of parvovirus B19 infection is available, it may not be possible to clinically exclude

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rubella or measles so the HCW should stay off work.103 The need for contact tracing of patients or other staff is determined by local risk assessment. Susceptible exposed staff working in defined

period of at least 15 days after the last significant contact.

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Rubella

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areas, such as antenatal services, should be considered for removal from direct patient care for a

Epidemiology

Rubella vaccination in the UK has reduced, but not eliminated, rubella; there were 65 confirmed cases of rubella in England and Wales in 2012.115 In countries without a vaccination programme,

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rubella is often endemic with periodic epidemics. A single dose of rubella-containing vaccine confers approximately 95–100% protection against rubella.116

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Transmission

Infection is generally spread by the respiratory route, but the virus has also been detected in blood,

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urine and faeces. Individuals are infectious from approximately seven days before to approximately seven days after rash onset.117 Asymptomatic or subclinical infection is common. Heseltine et al.118 described an outbreak of 14 cases and five probable cases of rubella amongst hospital HCWs in the context of a voluntary rubella immunization programme. Five of the cases were pregnant women seronegative for rubella, four of whom were in the first trimester of pregnancy. Two of the five cases developed rubella and one developed asymptomatic

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seroconversion. All three, and one other woman who was exposed to multiple cases, chose to terminate their pregnancies. In an outbreak that exposed 56 susceptible pregnant women in a large

and delivered uneventfully.119


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prenatal and family planning clinic, two women developed rubella at 27 and 38 weeks of gestation

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Rubella is usually a mild febrile rash illness in pregnant and non-pregnant adults and children. Infection during pregnancy can result in foetal death or congenital rubella syndrome, features of

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which include: cataracts/congenital glaucoma, congenital heart disease, hearing impairment, pigmentary retinopathy, purpura, hepatosplenomegaly, jaundice, microcephaly, developmental delay, meningoencephalitis and radiolucent bone disease.117 Risk of congenital rubella syndrome is greatest when infection occurs during the first trimester. Maternal rubella infection may result in

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foetal damage in up to 90% of infants during the first 11 weeks of gestation.120 Risk of foetal damage when infection occurs after 16 weeks of gestation seems to be low.120 There is also an

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association with prematurity.121


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At pre-employment assessment, all HCWs should be assessed for rubella immunity according to past immunization and/or rubella antibody status; seronegative non-pregnant HCWs should be vaccinated. Rubella immunity is assumed if a person has documented evidence of two or more doses of rubella vaccine, one dose of vaccine and one rubella-antibody-positive result, or two or more independent rubella-antibody-positive results. Pregnancy should be avoided for 28 days following measles-mumps-rubella (MMR) or other rubella-containing vaccines.122 Vaccination is

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contra-indicated in pregnancy but inadvertent vaccination is not an indication for termination. The pregnant woman should be counselled about the theoretical potential risk, but reassured that the ‘Vaccine in Pregnancy Registry’ of 226 women who received the RA 27/3 rubella vaccine within

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three months before or after conception all delivered healthy infants at term.123 Rubella vaccine virus has been detected in breast milk, but produced only mild or asymptomatic infection in the nursing infant.124,125 HCWs who remain susceptible to rubella during pregnancy should be

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immunized with MMR after delivery.67

Due to the frequently mild nature of the clinical illness, and sometimes absence of a

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characteristic rash, avoidance of exposure is difficult and infection may occur without awareness.

Post exposure care

Rubella-susceptible women should be tested for serological evidence of asymptomatic infection

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four weeks after exposure, or if a rash develops. After a contact, rubella-immune women can be reassured but reminded to report any rash illness.67 Human normal immunoglobulin (HNIG) has no proven benefit.

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The management of primary rubella or symptomatic rubella re-infection would depend on the stage of pregnancy. Consideration may be given to rubella polymerase chain reaction of

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amniotic fluid to ascertain if foetal infection has occurred.67

Impact on employment of infection or exposure in pregnancy HCWs with active rubella infection should be excluded from duty until seven days after the onset of rash. After exposure, susceptible personnel should be excluded from patient care from the seventh to the 21st day after last exposure.77

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Measles Epidemiology

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The majority of people born before 1970 have natural immunity to measles. A range of factors have resulted in a susceptible childbearing age cohort and recent measles outbreaks in the UK. Of 218 HCWs in a UK teaching hospital, 3.3% were found to be non-immune.126 There were 2030

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confirmed cases of measles in England and Wales in 2012.115 A single dose of measles has an estimated efficacy of 92%.127 Two doses of MMR should be given;128 this confers approximately

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99% protection.129

Transmission

Measles is highly infectious. It is generally spread by the airborne route and by direct contact with

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respiratory secretions of infected individuals, and less commonly by articles freshly soiled with respiratory secretions. Individuals are infectious from one day before the beginning of the prodromal symptoms (usually approximately four days before rash onset) until four full days after

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the onset of rash.130

With suboptimal immunization rates, healthcare settings have been shown to carry a high

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risk of measles transmission, sometimes higher than in the general adult population.131 There were six clusters of cases in UK hospitals between 1995 and 1999, of which three included cases in HCWs.126


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Morbidity from measles can be considerable in otherwise healthy non-pregnant individuals and severe in infants, pregnant women and the immunocompromised. Infection in pregnancy led to intra-uterine death and preterm delivery in 18 (31%) of 58 pregnant women with measles.132 In the

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same study, 35 (60%) women were hospitalized and two (3%) died of measles complications. Foetal loss and prematurity appear to be more likely in the first two weeks after the onset of

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rash.132 There is insufficient evidence for increased risk of congenital anomalies.133


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At pre-employment assessment, non-pregnant HCWs are recommended to receive MMR vaccine unless they can provide evidence of immunization or immunity to measles and rubella.128 MMR should not be given to pregnant women or women trying to conceive within the next three months, as the effect on the foetus is unknown.134 Susceptible women should be offered MMR after

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delivery. There is no evidence that the vaccine virus is secreted in breast milk. Pregnant HCWs should, if possible, avoid exposures to measles by consideration of exclusion in the outbreak setting.67 Patients suspected or confirmed to have measles need to be admitted into standard

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isolation and nursed with PPE, although the positive predictive value of a clinical diagnosis of

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measles is known to be poor outside of an outbreak situation.130

Post exposure care

Pregnant women displaying signs of measles or with a recent contact should see their general practitioner, midwife or obstetrician immediately.67 Contact with a maculopapular rash should prompt risk assessment for measles, rubella and parvovirus.67 The significance of a measles exposure should be gauged using a less stringent definition of a significant contact than that for

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VZV,67 and susceptibility should be assessed based on a combination of age, history of vaccination or infection and/or antibody screening.129 HNIG prophylaxis is recommended in certain settings to protect the mother against severe disease. HNIG is most effective if given within 72 h of exposure,

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but may be offered up to six days post exposure.135 HNIG is not always protective of infection in the newborn,136 and there is no evidence that HNIG prevents intra-uterine death or preterm delivery.133 All infants born to mothers in whom the rash appears six days before to six days after

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delivery should also receive HNIG.67 Measles vaccination can prevent or attenuate infection if given within three days of exposure, but is contra-indicated in pregnancy.130

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When serological diagnosis is confirmed, management of the pregnancy should continue as normal. Follow-up of the infant should be considered, even if congenital infection is not anticipated.67

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As HNIG is not 100% effective for the prevention of measles, HCWs who do not have evidence of immunity should be excluded from work from five days after exposure130 until the end of the

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Enteroviruses

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incubation period (18 days), or until no longer infectious if illness develops.

Epidemiology

Enteroviruses include multiple virus types, with infection either being asymptomatic or causing a range of illnesses, including non-specific fever, rashes (maculopapular and vesicular), meningitis, upper respiratory tract illness, conjunctivitis and poliomyelitis. Europe was declared polio free in 2002.137 Non-polio enterovirus infection is common worldwide. Outbreaks have been reported.

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Transmission Transmission is faecal-oral or through respiratory secretions, either directly or via fomites,

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depending upon the nature of the infection in the index case. Contaminated food and water are possible sources.

Outbreaks have been described within the healthcare environment, particularly in neonatal

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units138 and among immunocompromised patients,139 where clinical implications are more likely to

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be significant.


Pregnancy would not be expected to alter the course of enteroviral infection in the mother. Enteroviral infection during pregnancy has been associated with low birth weight and preterm

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infants,140 and with childhood-onset insulin-dependent diabetes mellitus,141 childhood autoimmune thyroiditis142 and intra-uterine death.143 Despite these associations, maternal infection is not normally expected to carry adverse consequences for the foetus.67 Infection with Coxsackie

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virus in pregnancy has been associated with the development of severe multi-system infection in

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the neonatal period.144

Post exposure care

Post exposure follow-up is rarely offered; instead, advice is given to pregnant women to report any relevant illnesses. Follow-up after infection may be appropriate, depending upon the clinical character of the infection. There are no known treatments or routinely available tests for preexisting immunity to non-polio enteroviruses.

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Healthcare worker protection Except for poliovirus, there are no vaccines available. Avoidance of contact is difficult due to the

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often asymptomatic nature of the infection, but transmission within healthcare facilities can be reduced through standard precautions including good hand hygiene. Infected people may excrete

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virus for many weeks.


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Employment restrictions are not recommended after exposure due the difficulties in defining susceptibility, likelihood of infection and any infectivity period. SICPs should limit transmission. HCWs should report all possible infective illness.

Mumps Epidemiology

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Other infections

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A combination of poorly effective vaccine, concerns about waning immunity in children after one dose of vaccine145 and suboptimal two-dose vaccine coverage has led to outbreaks in the UK and

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worldwide. There were 2564 confirmed cases in England and Wales in 2012.115

Transmission

Transmission is through direct contact with respiratory droplets or saliva, and through fomites. The infectious period is from several days before the parotid swelling to five days after onset.146

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Contagiousness is similar to that of influenza and rubella, but not as infectious as chickenpox or measles. Sporadic transmission and mumps outbreaks affecting HCWs have been reported in

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hospitals.147,148 In an investigation of mumps outbreaks in Tennessee in 1986–1987, 17 hospitals reported infection control problems caused by mumps.147 Most cases in HCWs were community

exposure.147

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acquired, but six HCWs in three different hospitals developed mumps following nosocomial

Pregnancy would not be expected to alter the course or the severity of the infection.149 Mumps in the first trimester can increase the rate of spontaneous abortion.150 Maternal mumps in the two weeks before delivery has been associated with neonatal thrombocytopenia,151 endocardial

Post exposure care

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fibroelastosis,152 mumps pneumonia153 and other causes of respiratory distress in the infant.154

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vaccination status.

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There is no effective PEP. HCWs should report any exposure or relevant illness, regardless of their

Healthcare worker protection Before employment, occupational health assessment should target non-pregnant susceptible HCWs for MMR vaccination. The observed effectiveness of a single dose of the mumps component of the MMR vaccine is 69%;155 two doses are recommended.156 For practical reasons, it is sensible to focus on vaccinating the group with the highest risk of susceptibility (i.e. adults born since

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1980).146 Evidence of protection would include documentation of having received two doses of MMR or a positive antibody tests for mumps immunoglobulin G. MMR vaccination is contraindicated in pregnant women; live-attenuated mumps virus has been recovered from the placentas

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of vaccinated women already scheduled for therapeutic abortion.157 Inadvertent vaccination should prompt counselling but is not an indication to terminate the pregnancy. Avoidance of exposure is difficult because of the infectious prodrome and high proportion of asymptomatic cases

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(approximately 30%). Patients suspected or confirmed to have mumps should be isolated for five days from the beginning of illness and nursed with respiratory precautions (gown and gloves)

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during patient contact.146


Hospital staff with clinical mumps infection should be excluded from work for five days from the

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onset of illness.146 A risk assessment for susceptible staff who are contacts of a case may indicate

Influenza Epidemiology

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the need for exclusion from patient contact.146

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The incidence of seasonal influenza A and B in temperate climates typically increases between late autumn and mid spring, with variable intensity depending, in part, upon the size of the susceptible population and degree of virus antigenic drift. Periodic pandemics occur when influenza A strains change significantly, but the severity and extent of influenza pandemics are difficult to predict.

Transmission

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Influenza is highly infectious and is spread by respiratory droplets, which are either inhaled or selfinoculated on to mucosal surfaces following contact with an infectious person or fomites. Healthcare-associated transmission of influenza has been well documented, including seasonal

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influenza and, more recently, 2009 pandemic influenza A H1N1, of which there were 30 documented cases from data accrued from 75 hospitals in the UK.158 Oseltamivir-resistant influenza A (H1N1) was transmitted to three patients who were present at the same time as the

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index patient on a medical ward without isolation procedures, but the four patients never shared rooms.159 An asymptomatic HCW was the suspected source of infection in a nosocomial outbreak

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of H1N1 at a Dutch hospital.160 There are conflicting data on the relative risk of occupational exposure. During the 2009 influenza A1(H1N1) pandemic, there was found to be no association between working in an acute care hospital and risk of influenza infection.161 Williams et al. found no association between HCW status and risk of influenza, but identified other risk factors such as

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the presence of children in the household.162


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In the 1918 and 1957 pandemics, and during the influenza A (H1N1) 2009 pandemic in the USA, pregnant women appeared to have an increased risk of influenza complications and mortality.163 In

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2009, they were found to be four times more likely to be hospitalized than the general population,164 and seven times more likely to die, once infected, compared with females of childbearing age with no underlying condition.165 Risks appear to be greatest in the third trimester and for women with underlying medical conditions such as asthma.163,165 Foetal risks are likely to be secondary to maternal and foetal inflammatory responses.166 Transplacental passage of influenza A H5N1 and H1N1 has been described.166,167 Risks include higher rates of spontaneous

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abortion and preterm birth, and associations have been suggested with congenital abnormalities168 and childhood leukaemia169

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Vaccination is the most effective deliverable means of prevention, and should be encouraged for all HCWs to reduce acquisition and transmission within healthcare premises.170 The inactivated

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trivalent vaccine is safe during pregnancy; one study of approximately 2000 immunized pregnant women demonstrated no adverse foetal effects.171 Uptake of seasonal influenza vaccine among

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HCWs is suboptimal at 45.6% in 2012/13.172 Other measures to reduce risk of infection from influenza, as per other respiratory tract infections, include isolation of infected individuals and deployment away from their care, appropriate use of PPE and good hand hygiene.173 Employers should risk assess and consider redeployment of the pregnant HCW (whether vaccinated or not)

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away from the direct care of those who have, or may have, influenza.174 Despite these measures, the wide spectrum of clinical presentations, including potential for asymptomatic carriage, will

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contribute to an ongoing risk of exposure.

Post exposure care

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Guidelines in relation to pandemic influenza state that pregnant HCWs, and women up to two weeks post partum with a history of exposure or who develop flu-like symptoms, should make early contact with health services for consideration of antivirals to commence within 48 h of symptom onset.175 Samples may be taken for diagnosis if in accordance with national guidelines, but swab results should not be awaited prior to commencement of therapy. In the absence of suspected oseltamavir-resistant isolates, symptomatic pregnant women who are not severely

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immunosuppressed are recommended to receive oseltamivir. Zanamivir is recommended as second-line treatment or if the patient is also severely immunosuppressed.175 Oseltamivir is also recommended as PEP for otherwise immunocompetent pregnant women who present within 48 h

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of last contact. Zanamivir would be the alternative when osteltamivir resistance is known or suspected, and provided that presentation is within 36 h of last contact.175 The US Food and Drug Administration has categorized oseltamivir and zanamivir as Pregnancy Category C. Amounts in

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breast milk are probably too small to be harmful.175 Pregnant HCWs should be advised to seek

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urgent medical attention should they develop signs or symptoms of complicated influenza.175


Following exposure, HCWs are not routinely excluded from clinical duty. Infected HCWs should

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be excluded until asymptomatic as per other causes of respiratory tract infection. 173

Conclusion

Protection of the pregnant HCW is the responsibility of the individual, antenatal care provider and

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employer, and is made possible through awareness of the risks and potential interventions both before and after exposure. The HCW should be made aware that risk of exposure extends to the

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home and community, and advised on protective behaviour. Consideration should be given to vaccination when it is safe, and reducing likelihood of exposure through universal precautions, infection control and redeployment where appropriate. If exposure or suspected exposure occur, or if the pregnant HCW develops an infective illness, urgent specialist advice should be sought to direct medical and occupational health management and laboratory investigation, considering viral and non-viral causes.

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Conflict of interest statement

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None declared.

Funding source

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None.

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Viral infections in pregnancy.

Viral infections during pregnancy: a guide for the emergency physician.

Routine advice against smoking in pregnancy.

Developing healthcare support workers.

Curbing Ebola infections among healthcare workers in West Africa: unconventional strategies needed.

Risk factors for bloodborne viral hepatitis in healthcare workers of Pakistan: a population based case-control study.

Mitophagy in viral infections.

Viral infections.

Hepatitis B vaccination policies for student healthcare workers in Europe.

The issue of mandatory vaccination for healthcare workers in Europe.

Pre-placement screening for tuberculosis in healthcare workers.

Healthcare workers and hepatitis B.

Influenza vaccination among healthcare workers in Italy.

Preventing occupational stress in healthcare workers.

Preventing occupational stress in healthcare workers.

Tuberculosis and Healthcare Workers in Underresourced Settings.

Hepatitis B immunization in healthcare workers.

Bordetella pertussis infection in paediatric healthcare workers.

Occupational allergy: respiratory hazards in healthcare workers.

Antibiotics for presumed viral respiratory infections.

T-cell therapy for viral infections.

Lactoferrin for prevention of common viral infections.

Antibiotics for presumed viral respiratory infections.

Advice on health care workers infected with HIV.