1. Systemic Infections in Pregnancy
Dr. Jasmin Sapanghila-Tamon

2. Varicella
Rubella
Hepatitis B
Syphilis
HIV

3. Varicella Infection

4. Varicella Infection DNA Herpesvirus
Primary infection causes varicella (chickenpox)
Recurrent infection causes herpes zoster (shingles)

5. Pathogenesis and Clinical Features
Incubation period days
Mild prodrome for 1-2 days
Maculopapular rash
generally appears first
on the head;
most concentrated on trunk

6. Mode of Transmission Direct Contact – with patient
who sheds the virus from
vesicles
Indirect Contact – through
articles fresh soiled by
discharges of infected
persons
Airborne – or spread by droplet
infection

7. Period of Communicability:
The patient is contagious about a day before the eruption of rashes and continuous to be so up to the 5th or 6th day after the last scab formation or until all vesicles have become encrusted.

8. Diagnostic Test:
Determination of V-Z virus though Complement Fixation Test
Determination of V-Z virus through Electron Microscopic examination of vesicular fluid

9. Complications:
Secondary infection of the lesions – furuncles, cellulites, skin abscess, erysipelas
Meningoencephalitis
Pneumonia
Sepsis

10. Groups at Increased Risk of Complications of Varicella
Normal adults
Immunocompromised persons
Newborns with maternal rash onset within 5 days before to 48 hours after delivery

11. Is risk of severe chickenpox increased in pregnancy?
No definite evidence that varicella is more likely to be fatal in pregnant women than in non pregnant adult
Hermmann KL. Clin Obstet Gynecol 1982;25:

12. Fetal Effects of Varicella
No infection
Infection
Congenital Varicella syndrome
Neonatal varicella infection
Infant herpes zoster

13. Transmission to the Fetus
<13 weeks AOG: 0.4%
13-20 weeks AOG: 2%
>20 weeks AOG: 0
Within 5 days before or after delivery: 10-20% neonatal varicella infection

14. Congenital Varicella syndrome
Damage to sensory nerves
Damage to optic nerve and lens vesicles
Damage to cervical
and lumbosacral
cord
Damage to brain

15. Diagnosis of Congenital varicella syndrome
Cordocentesis to estimate fetal VZV-specific IgM ab
Chorionic villus sampling to detect VZV DNA sequence using PCR
Serum AFP
UTZ

16. Management of the mother – Post exposure
Check VZV immunity
Consider
Prevention of chickenpox – VZIG
Treatment of chickenpox with antiviral
Counseling of mother and close fetal monitoring

17. Exposure Criteria for Use of VZIG:
Continuous household contact
Playmate/officemate contact >1hour indoors
Hospital contact – adjacent bed or infected staff member
Newborn of infected mother – from 5days before to 2days after delivery
AND
Time lapse from exposure is less than 96 hours 17

18. Varicella zoster Immunoglobulin (VZIG)
Prevent congenital varicella syndrome ?
No definite evidence
No congenital varicella syndrome among 97 pregnant women who received VZIG, but not sufficient power to reach significance
Documented cases of congenital varicella syndrome despite VZIG
Enders et al Lancet 1994: 343;

19. If patient is not pregnant but has a significant exposure to varicella
give vaccine within 120 hours of exposure
70-100% effective if given within 72 hours of exposure
Not effective if given beyond 5 days of exposure but will produce immunity

20. Treatment
Generally, there is no need to treat uncomplicated varicella since this is almost always a self-limiting disease.
Only in an immunocompromised host or when complications such as pneumonitis or encephalitis occur should antiviral therapy be considered.

21. Treatment For women infected with varicella
Give acyclovir 800mg 5 times a day for 5-7 days
Not recommended for routine use among otherwise healthy infants and children with varicella

22. Summary Chickenpox may be serious for pregnant women and fetus
Increasing numbers of seronegative women could result in increase chickenpox in pregnancy
Vaccine strategy should aim to protect all non immune adults especially women of reproductive age
Congenital varicella syndrome may be a rare occurrence, but the risk to the fetus is so high that prevention, post exposure prophylaxis and treatment, once infected, should always be an option.

23. Rubella

24. Rubella Highly communicable disease
Infected person may shed the virus in the upper respiratory tract from 1 week before to 5-7 days after the onset of rash
Incubation Period:
14 days (12-23 days)

25. Rubella
Low grade fever and mild upper respiratory tract infection Maculopapular rash on the face and neck, trunk and proximal extremities Development of adenopathy Rash fades within 1-3 days of onset

26. Incubation Period: 12-23 days
20%-50% of infections may be asymptomatic
Viremia precedes clinical signs by 1 week, and adults are infectious during viremia until 5-7 days of the rash

27. Rubella Risk of congenital defects: </=12 weeks AOG: 80%

28. Congenital Rubella Syndrome
Eye defects
Heart disease – PDA
Sensorineural deafness
CNS defects
Pigmentary retinopathy
Purpura
Hepatosplenomegaly and jaundice
Radiolucent bone disease

29. Rubella in Pregnancy
There is no treatment to ameliorate maternal disease or reduce the risk to the fetus when maternal infection is present
Prevention of fetal infection requires prevention of maternal infection through widespread vaccination programs

30. WHO Recommendation
All countries to assess their rubella status and introduce immunization and surveillance, if appropriate

31. Rubella Do serum rubella IgG on all pregnant patients
If patient is seronegative to rubella, give rubella vaccine postpartum

32. Counseling and Management
Pregnant women with confirmed rubella infection must have proper counseling about the risks and types of congenital anomalies

33. Counseling and Management
Routine use of rubella Ig is not recommended for postexposure prophylaxis since this does not prevent infection nor viremia.
Advisory Committee on CDC, Aug, 2006

34. Rubella Vaccine
Long term protection (about 15 years) from vaccination is about 98 to 99%; thus about 2% of vaccinated women may be negative when tested.
Ideally all vaccinated women should have their serological status determined before becoming pregnant.

35. Rubella Screening
MMR should not be given to adolescents who are known to be pregnant or to adolescents who are considering becoming pregnant within 3 months of vaccination.

36. Recommendations
Routine screening for rubella susceptibility by history of vaccination or by serology is recommended for all women of childbearing age at their first clinical encounter.
Susceptible non pregnant women should be offered rubella vaccination; susceptible pregnant women should be vaccinated immediately after delivery.
An equally acceptable alternative for non pregnant women of childbearing age is to offer vaccination against rubella without screening.

37. Hepatitis B

38. Caused by DNA hepadnavirus
Incubation period: 6 weeks to 6 months
Highest concentration in the blood, lower concentrations in other body fluids
Transmitted by percutaneous or mucous membrane exposure to infectious blood or body fluids that contain blood

39. Risk Factors 1. Persons of Asian, Alaskan, Sub-Saharan African descent
2. History of IV drug use
3. History of STD
4. Multiple sexual partners
5. Worker or patient in a hemodialysis unit
6. Health care or public safety worker

40. Risk Factors
7. Household contact with Hepatitis B carrier 8. Sexual contact with Hepatitis B carrier 9. Worker or residence in an instiution for the developmentally disabled 10. History of blood transfusion 11. Delivery to a carrier mother

41. Hepatitis B
Risk for chronic infection is inversely related to age at infection
In adults, approximately half of newly acquired HBV infections are symptomatic, 1% result in acute liver failure
90% of infants and 30% of children aged <5 years become chronically infected

42. Diagnosis HBsAg Total anti HBc IgM anti HBc Anti HBs Interpretation -
Never infected +
Early acute infection; after vaccination (18 days)
Acute infection
Acute resolving infection
Recovered from previous infection and immune
Chronic infection
Immune in conc >/= 10mIU/mL

43. Pregnancy and HBV Infection
Transmission of HBV from mother to infant (predominantly intrapartum) is one of the most efficient modes of HBV spread
4 Routes
1. Transplacental
2. Intrapartum
3. Post-partum
4. Breast milk

44. Pregnancy and HBV Infection
Perinatal Transmission Rates of Hepatitis B Virus
Clinical Status
Transmission Rate
HBsAg +, HBeAg -
10-20%
HBsAg +, HBeAg +
90%
Acute Hepatitis B first trimester
10%
Acute Hepatitis B third trimester
80-90%

45. Hepatitis B TREATMENT Acute Hepatitis B
primarily supportive on an ambulatory basis with bed rest
High protein diet
Avoidance of hepatotoxic drugs

46. Treatment of Hepatitis B
Chronic Hepatitis B Goals of therapy 1. Suppression or complete resolution of chronic active hepatitis 2. Halting progression of liver disease 3. Converting patients to a non-infectious state

47. Prevention Hepatitis B immune globulin (HBIG) Hepatitis B vaccine
0.06mL/kg
Hepatitis B vaccine
Periodic testing to determine ab levels in immunocompetent persons is not necessary, and booster doses of vaccine are not recommended

48. Hepatitis B CDC National strategy to eliminate transmision of HBV
Prevention of perinatal infection
Routine infant vaccination
Vaccination of previously unvaccinated children and adolescents through age 18
Vaccination of previously unvaccinated adults at increased risk for infection

49. Hepatitis B Post-Exposure Prophylaxis
Percutaneous or mucosal exposure to HbsAg (+) blood or body fluids that contain blood
Administer Hepatitis B vaccine and Hepatitis B Ig
Sexual or needle sharing contact of an HbsAg (+) person
Victim of sexual assault/abuse of a perpetrator who is HbsAg (+)

50. Hepatitis B Post-Exposure Prophylaxis
Victim of sexual assault/abuse of a perpetrator with unknown HbsAg status
Administer Hepatitis B vaccine
Percutaneous or mucosal exposure to HbsAg (+) blood or body fluids that contain blood from a source with unknown HbsAg status

51. Management of HbsAg (+) Persons
Persons with chronic HBV infection should be referred for evaluation of CLD
Household, sexual and needle-stick sharing contacts of chronically infected persons should be identified
Sexual partners should be counseled to use methods to protect themselves from sexual exposure to infectious body fluids
Protect liver from further harm

52. Syphilis

53. Syphilis Caused by the spirochete Treponema pallidum
Acquired by sexual contact
3-10% contract the disease from a single sexual encounter with an infected
partner

54. Stages Primary – genital &extragenital
Secondary – bacteremia involving all major organs
Latent – lack of clinically apparent disease
Tertiary – 1-20 years after the disease has become latent, progressive damage involving CV, muskuloskeletal and CNS

55. Syphilis Primary Syphilis Chancre – hallmark lesion
Typically single, painless ulcer with raised rounded borders and a “clean” indurated base arise at the site of entry of T.pallidun into the body, inapparent breaks
in the host’s skin
during intercourse

56. Secondary syphilis

57. Diagnosis
Dark field microscopy of secretions from chancre demonstrate the spirochetes

58. Diagnosis Non Treponemal Tests: VDRL, RPR - screening tests
- correlates with disease activity
- use to assess treatment
response

59. Diagnosis Treponemal Tests: FTA-ABS, TPHA - confirmatory test
- remains positive for the
remainder of the patients’ lives
regardless of treatment or
disease activity

60. Fetal and Neonatal Infections
Spirochetes readily cross the placenta causing congenital infection
Hepatomegaly, anemia, thrombocytopenia, ascites and hydrops
High serologic titers and unknown duration of infection are major predictors of congenital syphilis

61. Treatment
Penicillin G is the treatment of choice for all stages of syphilis
No proven alternatives to penicillin therapy during pregnancy
Jarisch-Herxheimer reaction
- acute febrile reaction frequently accompanied by headache, myalgia, and fetal heart deceleration
- usually occur within the first 24 hours after treatment

62. Management of Sex Partners
Persons exposed within 90 days before the diagnosis of primary, secondary or early latent syphilis must be treated presumptively
If exposed >90 days before the diagnosis, treat presumptively if the serologic test result is not immediately available and follow up is uncertain
Long term partners of patients with late latent syphilis should be evaluated clinically and serologically and treat on the basis of the findings

63. Follow up
Patients should be reexamined clinically and serologically using non treponemal test titers 3,6,12, and 24 months after treatment
Failure of nontreponemal test titers to decline 4-fold within 6 months after treatment might be indicative of probable treatment failure
For retreatment, give Penicillin G x 3doses

64. HIV

65. Introduction Human Immunodeficiency Viruses DNA retroviruses
HIV-1 and HIV-2
most cases are caused by HIV-1 infection
mode of transmission
sexual intercourse: major mode of transmission
blood or blood-contaminated products
mothers may infect their fetuses

66. Pathogenesis
thymus-derived lymphocytes, T lymphocytes, defined phenotypically by the CD4 surface antigen, are the principal target
CD4 site serves as a receptor for the virus
co-receptors are necessary for infection
chemokine receptors – CCR5 and CXCR4

67. Pathogenesis
after initial infection, the level of viremia usually decreases to a set point
patients with the highest viral burden at this time progress more rapidly to AIDS and death
over time, the number of T cells drop insidiously and progressively --- results in profound immunosuppression

68. Clinical Manifestations
Incubation period: days to weeks
acute illness
similar to many viral syndromes
lasts less than 10 days
common symptoms: fever, night sweats, fatigue, rash, headache, lymphadenopathy, pharyngitis, myalgias, arthralgias, nausea, vomiting and diarrhea

69. Clinical Manifestations
AIDS
HIV-positive assay results associated with any number of clinical findings
CD4+ count of less than 200/mm3
generalized lymphadenopathy, oral hairy leukoplakia, aphthous ulcers, and thrombocytopenia
neurologic disease is common

70. Clinical Manifestations
opportunistic infections:
esophangeal or pulmonary candidiasis
persistent herpes simplex, zoster lesions
condyloma acuminata
tuberculosis
cytomegalovirus pneumonia, retinitis or gastrointestinal disease
molluscum contagiosum
Pneumocystis pneumonia
toxoplasmosis

71. Serological Testing Standard Testing Protocol
Enzyme Immunoassay (EIA) – used as a screening test for HIV antibodies
repeatedly positive screening test has a sensitivity of more than 99.5%
positive test is confirmed with either Western blot or immunoflourescence assay (IFA)

72. Maternal and Fetal-Neonatal Infection
mother-to-child transmission accounts for most pediatric HIV infections
pregnancy rates among women with HIV infection increased significantly in the current era

73. Maternal and Fetal-Neonatal Infection
transmission rates
20% before 36 weeks
50% days before delivery
30% intrapartum
30-40% during breastfeeding

74. Maternal and Fetal-Neonatal Infection
Vertical transmission is more common in preterm births, especially if with prolonged membrane rupture
3.7 relative risk for intrapartum viral transmission

75. Maternal and Fetal-Neonatal Infection
transmission at birth was increased from 15 to 25% in women whose membranes were ruptured for more than 4 hours
placental inflammation and chorioamnionitis may increase HIV -1 transmission by 3%

76. Management during Pregnancy
counseling is mandatory
should be started early in pregnancy
antiviral therapy
therapeutic goal: maximal and enduring suppression of viral load and restoration and preservation of immunologic function
therapy should be offered to all HIV-infected pregnant women regardless of CD4+ T cell count or HIV RNA level

77. Management during Pregnancy
antiviral therapy (generally)
Symptomatic
severe symptoms of HIV
AIDS
CD4 count 200cells/mm3 or less
Viral load 1,000 copies/ml or greater

78. Management during Pregnancy
Antiretroviral agents:
nucleoside reverse transcriptase inhibitors
non-nucleoside reverse transcriptase inhibitors
protease inhibitors
fusion inhibitors – block HIV-1 cell membrane binding and cell entry

79. Management during Pregnancy
measurement of CD4+ T-cell count approximately every trimester, or about every 3-4 months
HIV RNA levels should be monitored 4 weeks after initiation of treatment, then monthly until undetectable, then every 3 months, and finally near term
monitor for antiretroviral toxicities during the initial 1-2 months of treatment
surveillance for hepatic toxicity and lactic acidosis

80. Management during Pregnancy
treatment failures
nonadherence
inadequate drug potency
suboptimal levels of antiretrovirals
viral resistance

81. Management during Pregnancy
additional medical care
hepatitis B, influenza, and pneumococcal vaccines are given after viral suppression
therapies for opportunistic infection and tuberculosis
if CD4+ T-cell count is below 200/mm3, primary prophylaxis for P. carinii pneumonia is recommended (sulfamethoxazole-trimethoprim, dapsone)

82. Prevention of Vertical Transmission
2 principal approaches:
1. antiretroviral therapy
2. cesarean delivery

83. Prevention of Vertical Transmission
TIME OF ADMINISTRATION
ZIDOVUDINE REGIMEN
Antepartum
100 mg orally five times daily,
initiated at 14 to 34 weeks and continued throughout pregnancy
Intrapartum
intravenous zidovidine in a 1-hr initial dose of 2 mg/kg, followed by a continuous infusion of 1 mg/kg/hr until delivery
Neonate
give syrup at 2 mg/kg every 6 hours for 6 weeks, begin at 8 to 12 hours after birth

84. Prevention of Vertical Transmission
Cesarean Delivery
vertical transmission was reduced by one half when cesarean section was compared with vaginal delivery
when antiretroviral therapy was given along with cesarean delivery, the likelihood of transmission was reduced by 87%

85. Prevention of Vertical Transmission
Cesarean Delivery
scheduled cesarean delivery should be discussed and recommended for HIV-infected women whose HIV-1 RNA load exceeds 1000 copies/ml
recommended at 38 weeks

86. Breastfeeding not recommended
the probability of transmission per liter of breast milk ingested is estimated to be similar in magnitude to heterosexual transmission with unsafe sex in adults
risk is related to maternal HIV RNA level, HIV disease status, breast health, duration of breastfeeding
most transmission occur in the first 6 months

87. Post partum
otherwise healthy women with normal CD4+ T cell counts and low HIV RNA levels may discontinue treatment after delivery
close monitoring
pyschologic support is important

88. Postpartum Contraception
All HIV infected individuals should be counseled to use condoms consistently
OCP – significantly interact with
amprenavir/
fosamprenavir,
efavirenz, lopinavir,
nelfinavir, nevirapine,
and ritonavir
IUD