PERICONCEPTION MANAGEMENT OF INFECTIOUS DISEASES - JUNE

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1 PERICONCEPTION MANAGEMENT OF INFECTIOUS DISEASES - JUNE 2017 Julie van Schalkwyk, MD FRCSC Associate Clinical Professor, University of British Columbia Obstetrics and Gynecology BCWH Disclaimer No Conflicts of Interest 1

2 Overview HBV Epidemiology, health implications Perinatal risks, current Post-exposure Prophylaxis (PEP) Review evidence for use HBV antivirals in pregnancy Updated treatment recommendations HCV Epidemiology, testing Novel HCV therapeutics ZIKV Congenital effects Conception timing Disease Models of Chronic Hepatitis B 2

3 HBV Epidemiology One third of global population (2 billion) acutely infected 300 million chronic carriers 34 million HIV infected and 185 million HCV infected 45% of the world live in high endemic areas, with lifetime infection risk >60% Only 12% live in low-endemic areas Up to 5% of mothers are chronic carriers WHO Weekly Epidemiological Record 2009, CDC Epidemiology and Prevention of Vaccine Preventable Diseases, 11 th Ed, 2009 Global Prevalence of Chronic HBV Infection 2006, 27% BC population identified as Asian descent CDC

4 Epidemiology - Canada prevalence - chronic Hep B ~0.5 1% in the general population varies in different populations immigrants: 8% Inuit: 6.9% First Nations: 0.3% STI clinic patients: 0.3% BC ~1% pregnant population HBsAg positive Canadian Guidelines on Sexually Transmitted Infections. PHAC Canadian Census report, 2006 HBV and HCC Chronic HBV is the most common cause of HCC 50% cases world wide 80% of cases in high endemic areas HCC is the 6 th most common cancer and the third most common cause of cancer death With CHBV infection 20-25% lifetime risk of dying from HCC or related liver diseases 600,000 die every year from complications related to chronic HBV Davis GL et al. Proc (BUMC) Parkin DM et al. CA Cancer J Clin

5 HBV testing in pregnancy HBsAg testing is part of routine prenatal screening panel Estimated that >90% of samples are tested Samples historically to BCCDC, private labs offer testing BCCDC performs reflex HBeAg testing on all HBsAg positive samples counseling maternal neonatal follow-up All new HBsAg positive samples that get reported to public health initiate public health nurse contact with individual to discuss PEP and follow-up at 9-12 mos post-partum Transmission percutaneous IVDU occupational blood exposure, transfusion blood products sexual anal>vaginal>oral horizontal household contact Perinatal in high endemic areas, most common mode of transmission the age of infection is inversely proportional to degree of chronicity 5

6 Neonatal PEP (Post-Exposure Prophylaxis) Perinatal transmission extremely efficient 80-90% Passive and Active Regimens HBIG alone 75% short term efficacy Vaccine alone 75% long-term efficacy HBIG and Vaccine Series 85-95% long term efficacy MMWR 2006, Vol 55 6

7 26 studies, 3622 women Efficacy and safety Lamivudine, Telbivudine, Tenofovir Antiviral therapy reduced perinatal transmission risk ratio 0.3, 95% CI No significant differences in congenital malformation, PTB or Apgar scares Tenofovir FDA Category B drug no HBV resistance development Cost Effective? For every 100 women treated, 9.7 cases of perinatal transmission is prevented Cost savings of $5184 per 100 women treated Fan et al., Obstet Gynecol 2014 For every 1000 women treated, $337,000 was saved, 314 quality-adjusted life years were gained and 21 cases of hepatocellular carcinoma and 5 liver transplants would be prevented Nayeri et al., Am J Obstet Gynecol

8 What about amniocentesis?? Recommendations All pregnant women should be screened for hepatitis B virus infection at their first prenatal visit by determination of their hepatitis B surface antigen IA and hepatitis B surface antibody status, regardless of previous testing or immunization. Obstetric-care providers should arrange for hepatitis B e antigen, hepatitis B virus (HBV) DNA level, alanine aminotransferase and ultrasound of the liver for all hepatitis B surface antigen-positive pregnant patients and arrange for specialist referral (see below) for the purposes of maternal health and perinatal HBV transmission risk stratification. NB In BC Consider 1 st trimester HBV DNA and a repeat with GDM screen ~26 weeks Coffin and Fung, Can J Gastroenterol Vol 26 No 12, December 2012 EASL Clinical Practice Guidelines J Hepatol 2012, Dionne-Odom et al, SMFM Consult Series #38 AJOG Oct

9 Recommendations Vaccinate for hepatitis B and give hepatitis B immunoglobulin within the first 12 hours of life to all neonates born to women who are hepatitis B surface antigen-positive Encourage families to complete the infant immunization series for hepatitis B virus according to local infant vaccination schedule and obtain serological confirmation of protection after completion of hepatitis B vaccination series, no sooner than 9-12 months of age In collaboration with an Adult infectious diseases/gastroenterology or hepatology specialist, consider antiviral treatment for viral suppression for prevention of perinatal transmission in women with hepatitis B DNA viral loads level >200,000 IU/mL (>10 6 copies/ml), starting at weeks of gestational age and continuing until delivery Coffin and Fung, Can J Gastroenterol Vol 26 No 12, December 2012 EASL Clinical Practice Guidelines J Hepatol 2012, Dionne-Odom et al, SMFM Consult Series #38 AJOG Oct 2015 HEPATITIS C AND PREGNANCY Novel therapeutic 9

10 Hepatitis C virus Enveloped, positive, single-stranded RNA virus Mutates within the host and between hosts- NO Vaccine! Global sero-prevalence % 185 Million infected globally 0.5%-1% sero-prevalence in pregnancy in B.C Perinatal transmission rate - 7.9% If HCV RNA pos - 9.5% (110/1155) Transmission correlates with high VL Moradpour et. al., Nature Reviews, Vol 5. June 2007 Blasig et al. 2. M Kuo, D Money, et al. JOGC June 2014, HCV Infection Transmitted through blood Needle sharing Contaminated blood products Tattoos, piercings Perinatal transmission 55-85% infected develop chronic HCV 15-30% will develop cirrhosis in 20 yrs Up to 500,000 die annually related to HCV compiications 10

11 HCV Diagnostic Algorithm Based on Serologic Testing Anti-HCV Antibody Positive HCV RNA Positive HCV Genotype+HCVVL Consider Fibroscan Vaccinate for HAV / HBV* Negative Negative No Further Testing No Active Disease *If patient lacks pre-existing antibodies to HAV or HBV. HAV=hepatitis A virus, HBV=hepatitis B virus. HCV RNA testing should be performed in Patients with unexplained liver disease whose anti-hcv test is negative and who are immunocompromised or suspected of having acute HCV infection Ghany MG, et al. Hepatology. 2009;49: HCV Patients Are Typically Infected With 1 of 6 Viral Genotypes Nucleotide sequences between the 6 major genotypes differ by 30% 35% Type and duration of therapy is different for the various Genotypes Subtypes (1a vs 1b) typically differ from each other by 20% 25% 1 Simmonds P. J Gen Virol. 2004;85:

12 Canadian HCV Population and Epidemiology Patient demographics % of HCV Prevalent Population >65 12% Age % <39 17% 1 64% Genotype 2,3 34% (14%, 20%) 4,5,6 <2% Myers et al., Can J Gastroenterol Hepatol Vol 28 No 5 May 2014 PHAC report, 2007 CROI

13 CROI

14 Who to Screen for Hepatitis C? Hx of blood products prior to 1990 IDU Multiple sexual partners Tattooing, body piercing Elevated abnormal liver function tests-even with no risk factors (HAV, HBV,HCV) Immigrants from high risk countries All pregnant women in BC? 2017 Canadian Task Force on Preventive Health Care does NOT support routine screening for all, DOES support screening of pregnant women Summary HBV HCV HBV DNA for all HBsAg positive Refer if VL> 200,000 IU/mL Tenofovir weeks to delivery Linkage to adult HBV care Evaluate, educate, vaccinate Novel therapeutics HCV screening in those at risk HCV screening for all pregnant women Linkage with adult HCV care RISK REDUCE with INTRAPRTUM MANAGEMENT 14

15 Date / time CDC ZIKV Global Map >60 countries Millions infected Tens of thousands laboratory confirmed 15

16 Zika VIRUS (ZIKV) infection Incubation period 3-12 days Viremia 3-5 days - saliva and urine > a week IgM Ab evolves thereafter 80% of those infected asymptomatic 20% mild disease (acute fever, maculopapular rash, arthralgia, myalgia, headache, conjunctivitis) ~ 1 week Associated with Guillain Barre Syndrome risk 1/4000 Neurologic sequelae of ZIKV broader than thought PHAC women PCR + in pregnancy 7% resulted in fetal death 117 infants born to 116 women with ZIKV +PCR 42% newborns gross clinical and/or brain imaging abnormalities 1 st trimester 55% 2 nd trimester 52% 3 rd trimester 29% 16

17 December pregnancies Suspected ZIKV infection (IgM) 6% infants born with signs consistent with Congenital ZIKV Syndrome 11% infants affected if maternal infection in first trimester Supports ongoing efforts to screen for ZIKV in pregnancy Local and Travel ZIKV Acquisition 214 locally acquired Florida 6 locally acquired Texas 17

18 PHAC Surveillance Data No locally acquired vector transmissions in Canada Congenital ZIKV Syndrome Microcephaly Intracranial calcifications Ventriculomegaly Abnormal gyri development Cortical atrophy Hypoplasia of cerebellum Hypertonia Hypotonia Spasticity Seizures Irritability Hyper-reflexia 18

19 WHAT IS A PREGNANCY CARE PROVIDER TO DO? Travel Recommendations Talk to your patients and partners about travel plans and history Pregnant women or women planning to become pregnant advise NOT to travel to countries with active ZIKV transmission If travelling long pants and sleeves Sleep in screened in/ air conditioned room DEET, picaridin and IR3535 safe in pregnancy PHAC November

20 Pregnancy Delay Post Travel Delay conception 2 months if the woman was the traveller Male partner travel condoms /abstinence duration of pregnancy, delay conception 6 months post travel Serologic/sperm testing of asymptomatic men for ZIKV not currently supported PHAC November 2016 Sperm washing/iui considered degree of risk reduction unknown Who to test? Anyone symptomatic with a travel history to the affected areas where symptoms developed 3 days after arrival to 14 days after return Anyone symptomatic & exposed (ie sexual) to a confirmed case within 3 days post exposure to 14 days after last exposure PHAC

21 Who to Test in Pregnancy? 1. Acute signs and symptoms compatible with Zika virus with travel or exposure history 2. A fetus suspected of having a congenital anomaly consistent with viral infection 3. Consider testing in asymptomatic pregnant travellers Counseling regarding unknown sensitivity and specificity of IgM, prolonged turnaround time for results, unknown sensitivity and specificity of ultrasound diagnosis PHAC 2016 How to Test SYMPTOMATIC: ZIKV RT PCR (blood/urine) within 10d of symptom onset: ZIKV IgM if >10d since symptom onset ASYMPTOMATIC PREGNANT: ZIKV IgM 2 (4) weeks post exposure (*NML recommendation) If IgM positive must be confirmed as ZIKV as much cross reaction with other flaviviruses such as Dengue 21

22 National Microbiology Laboratory TAT (Turn Around Time) PCR minimum 5 business days IgM ELISA minimum 7 business days PRNT (Plaque Reduction Neutralization Test) minimum 14 business days after ELISA result MANY IgM requests being returned until further details provided READ THE FINE PRINT! travel location and dates Clinical symptoms/signs Gestational age at time of travel ZIKV local transmission risk from returning travellers - July 22

23 Summary Congenital ZIKV in 6-55% of those infected Talk to your patients about travel Testing algorithms PROVIDE TRAVEL AND PREGNANCY INFO ON REQ!! Call or refer to MFM, RID/ID PLEASE REPORT New information is constantly emerging Laboratory testing capabilities will expand Thank you Dr. Neora Pick Dr. Deborah Money 23