Chapter 58. INFECTIONS

June 29, 1998
1st-year resident Kyong-bong Cha M.D

I. Instructions

  • Immunosurveilence decreased during pregnancy

    A. Fetal and newborn immunology

    ① Compromised compared with that of older children and adults

    ② Begin to develop by 9 to 15 weeks

    ③ Passive immunity : by IgG transferred actively across the placenta

    B. Neonatal infection

    ① Difficult to diagnosis

    ② If infected in utero, there may be depression and acidosis at birth

    ③ Symptoms and signs: suck poorly, vomit, abdominal distension,
    ? ? ? respiratory difficulty similar to idiopathic respiratory distress syndrome,
    ? ? ? lethargic or jittery, hypothermia rather than hyperthermia

    C. Risk factors of neonatal infection

    ① Preterm rupture of membrane

    ② Prolonged labor

    ③ Manipulations

    D. Causes of Fetal and Neonatal Infections

  • Infection occurring at less than 72hours of age ;caused by bacteria acquired in utero or during delivery

    II. Viral Infection

    A. Varicella-Zoster

  • DNA herpesvirus : remains latent in the dorsal root ganglia after primary infection
  • Most adults have acquired chicken pox during children and are immune
  • Infection is especially severe during pregnancy
  • Acyclovir : not teratogenic , but its use is reserved for life-threatening infection
  • Little evidence that zoster caused congenital malformation

    1. Prevention

    1. Varicella-zoster immunoglobulin (VZIG) to exposed susceptible individuals within 96hours
    2. An attenuated live-virus vaccine : not recommended for pregnant woman

    2. Fetal effect

  • when maternal chicken pox during early pregnancy severe congenital malformations including chorioretinitis cerebral cortical atrophy, hydronephrosis and cutaneous and bony leg defects

  • Varicella infection during pregnancy

    1. During the first 20weeks : absolute risk of embryopathy is about 2%

    2. After 20weeks : no clinical evidence of congenital varicella infection

    3. The highest risk is between 13 and 20weeks : 2 % of congenital varicella

    4. Later in pregnancy : associated with congenital varicella lesions , zoster occasionally develops at several months of age

    5. Fetal exposure to the virus just before or during delivery

      (before maternal antibody has been formed)

      ; serious threat to the newborn

  • Neonatal varicella infection

    ⒜ Incubation period : less than 2weeks

    ⒝ May develop disseminated visceral and CNS disease

    ? ? : commonly fatal

  • Varicella-zoster or zoster immunoglobulin (ZIG) should be administered to the neonate whenever the onset of maternal clinical disease was within 5days before delivery or 2days postpartum

      B. Influenza

    • Caused by members of the orthomyxoviridae family
    • Develops during winter epidemics
    • Self-limited and not life-threatening for otherwise healthy adults
    • If pneumonia develops, the prognosis becomes serious
    • When pneumonia develops , the mortality of pregnancy women is 27-50%

      1. Prevention

      1. Vaccination : safe for pregnant women, regardless of the stage of pregnancy
      2. Amantadine : if given prophylactically during epidemics , it is 70 to 90 % effective in preventing influenza

      2. Fetal Effect

      1. No congenital malformation
      2. Predispose to schizophrenia in later life : controversial

      C. Mumps

    • Uncommon adult infectious disease caused by an RNA paramyxovirus ; 80-90% seropositive
    • Infects the salivary glands, the gonads, meninges, pancreas and other organs
    • During pregnancy : no more severe than in nonpregnant adult

      1. Vaccination : the live attenuated Jeryl-Lynn vaccine is contraindicated
      2. Treatment ; symptomatic
      3. Fetal Effect : no evidence of fetal wastage

      D. Rubeola (Measles)

    • Most adults are immune to measles
    • Not appear to be teratogenic
    • Maternal measles : increased frequency of abortion and low birth weight infants
    • If the woman develops measles shortly before birth : considerable risk of neonatal infection and some risk of death
    • Passive immunization : immune serum globulin within 3days of exposure
    • Vaccination is not done during pregnancy

      E. Respiratory viruses

    • Ause the common cold, pharyngitis, laryngotracheobronchitis, bronchitis and pneumonia

      Major cause of common cold : Rhinovirus, coronavirus, and adenovirus

      1. Rhinovirus and coronavirus : RNA viruses , trivial self-limited illness rhinorrhea, sneezing, congestion
      2. Adenovirus ; DNA virus, cough , and lower respiratory tract involvement

    • Mothers suffering from common cold ; 4-5times increased risk of anencephaly
    • Adenoviral infection ; common cause of childhood myocarditis

      F. Enterovirus infection

    • Poliovirus, coxsackievirus, and echovirus
    • Cause CNS ,skin, heart and lung infection
    • May cause fetal infection
    • Risk factor for childhood -onset diabetes

      1. Coxsackievirus

    • Usually clinically inapparent but may cause aseptic meningitis, polio-like illness , rashes, respiratory disease , pleuritis, pericarditis and myocarditis
    • Can be a serious complication of pregnancy : can be fatal to fetus-infant
    • Viremia may cause hepatitis, myocarditis , and encephalomyelitis : which can cause fetal death
    • Clinical chorioamnionitis ; fetal ventriculomegaly and cardiomyopathy

      2. Poliovirus

    • Can cause paralytic disease ; poliomyelitis
    • Pregnant women not only were susceptible to polio but had a higher death rate
    • With the widespread use of vaccination during child hood, polio has become rare
    • Vaccination for susceptible pregnant women who must travel to endemic area or in other high risk situations

      G. Parvovirus

    • Causes erythema infectiasum, or fifth disease
    • Clinical feature ; a bright red macula , rash and erythroderma : slapped cheek
    • Maternal hydrops syndrome: preeclampsia-like disease related to large placental mass with fetal hydrops

      1. Fetal effect : abortion, fetal death , myocardial damage congenital anomalies by first -trimester pavovirus infection

      2. Diagnosis : confirmed serologically by Ig M-specific Ab

        for woman with positive serology, ultrasonic examination is indicated
        : if there is hydrops then fetal transfusion should be considered

      H. Rubella

    • Responsible for inestimable pregnancy wastage and severe congenital malformations

      1. Prevention ; to eradicate the disease completely

      1. Education of health -care providers and the general public on the danger of rubella infection
      2. Vaccination of susceptible women as as part of routine medical and gynecological
        care, including college health service
      3. Vaccination of susceptible women visiting family planning clinics
      4. Identification and vaccination of unimmunized women immediately after childbirth or
      5. Vaccination of nonpregnant susceptible women identified by premarital serology.
      6. Vaccination of all susceptible hospital personnel who might be exposed to patients
        with rubella or who might have contact with pregnant women

    • Rubella vaccination should be avoided shortly before or during pregnancy because the vaccine is an attenuated live virus

      2. Diagnosis

    • Abscence of rubella antibody is positive indicates susceptibility

      1. If maternal rubella antibody is positive at the time of exposure to rubellaor before

        -> the fetus will not be affected

      2. Antibody response after rubella infection

        1. Peak titer : 1 to 2 weeks after the onset of the rash
        2. Specific IgM antibody by radioimmunoassay : peak at 7 to 10days after onset of clinical disease persist for 4 weeks after appearance of the rash

      3. Congenital Rubella Syndrome

    • Rubella is a potent teratogen
    • As the duration of pregnancy increased , fetal infections are less likely to cause congenital malformations.
    • Include one or more of the following

      1. Eyelesions including cataract, glaucoma, microphthalmia and various other abnormalities
      2. Heart disease, including PDA, septal defects and pulmonary artery stenosis
      3. Gensorineural deafness
      4. CNS retarded fetal growth
      5. Thrombocytopenia and anemia
      6. Hepatitis, hepatosplenomegaly, and jaundice
      7. Chronic diffuse interstitial pneumonitis
      8. Osseous changes
      9. Chromosomal abnormalities

    • Infants born with congenital rubella

      -> May shed the virus for many months

      -> May be a threat to other infants as well as susceptible adults

      I. Cytomegalovirus

    • Most common cause of perinatal infection
    • 0.5 to 2 percent of all neonates
    • Transmitted horizontally by droplet infection and contact with saliva and urine. vertically from mother to fetus-infant and as s sexually transmitted disease.
    • Usually by 2 to 3 years of age children acquire the infection

      1. Maternal infection

      1. No evidence that pregnancy increased the risk or clinical severity of maternal cytomegalovirus infection,
      2. Symtomatic among about 15% of adult : fever,pharyngitis, lymphadenopathy, and polyarthritis

      2. Congenital infection : cytomegalic inclusion disease

      1. Low birth weight , microcephaly , intracranial calcifications ,chorioretinitis, mental and motor retardation, sensorineural deficits, hepatosplenomegaly, jaundice, hemolytic anemia and thrombocytopenic purpura
      2. About 20% of infants in the primary infection group had symptomatic infection at birth
      3. Primary infected mother

        ① 20% had symptomatic infection at birth

        ② After some years , sequella were identified in 25%

        ③ Less than 70 IQ ; 13% when childhood

        ④ Gensorineural hearing loss ; 15%

      3. Management

    • No effective therapy for maternal infection
    • Gerologic screening during pregnancy : limited value

      1. does not allow accurate predictability of the sequelae of primary infection
      2. there is no vaccine
      3. 1 -2 % of all infants excrete CMV and attempts to identify and isolate them are expensive and impractical

    • Asymptomatic CMV excretion; 10% of pregnant women
    • Primary infection ; diagnosed by fourfold increased Ig G titers
      by detecting IgM CMV antibody in maternal serum
    • Fetal outcome depends on the stage of gestation during which primary infection is documented

      4. Prenatal diagnosis

    • Microcephaly, ventriculomegaly, or cerebral calcifications by ultrasonogram, CT, or MRI
    • Confirmed by amnionic fluid culture
    • Cordocentesis to detect Ig M

      II. Bacterial Infections

      A. Group A Streptococcus

      1. Streptococcus pyogenes: rarely encountered today, virulent,
        produce a number of toxins and enzymes
      2. Toxic shock syndrome ; fatal
      3. Scarlet fever
      4. Erysipelas : acute streptococcal skin infection

      B. Group B streptococcus

    • Asymptomatic carriage of group B -hemolytic streptococcus

      :common in the vagina and rectum among 15-20 % of pregnant women between 23 and 26weeks

    • Adverse pregnant outcome: preterm labor , sepsis, PROM, chorioamnionitis ,puerperal sepsis, fetal and
      maternal infection

      1. Epidemiology

      1. Half of newborn of carrier women become colonized almost immediately at birth

        -> may lead to severe neonatal sepsis soon after birth

      2. The overall attack rate of early -onset sepsis

        1. 1-2/1000 of all births
        2. 10/1000 for babies born to colonized mother
        3. 40/1000 if there is preterm labor and delivery,prolong membrane rupture, or intrapartum fever.

      2. Neonatal sepsis

      ⑴ Septicemia from group B streptococci ; early onset disease

      ① Usually develop within 6 to 12 hours of birth

      ② Respiratory distress, apnea, shock

      ③ Mortality rate ; 25%

      ④ Neurologic sequelae; common

      ⑵ Late-onset disease

      ① Manefests as meningitis a week or more after birth

      ② Mortality rate ; less than early -onset sepsis

      ③ Neurologic sequelae are common

      3. Screening for maternal group B streptococcal carriage

    • controversial
    • Instead of screening ,intrapartum administration of ampicillin, penicillinG or Erythromycin based on the presence of risk factors is recommended

      Risk factors ;

      1. Preterm labor
      2. Preterm prematurely ruptured membranes
      3. Prolonged membrane rupture defined as greater than 18hours
      4. Sibling affected by symptomatic group B streptococcal infection
      5. Intrapartum maternal fever

      4. Treatment and prophylaxis

      1. Penicillin G prophylaxis at birth; lower incidence of streptococcal disease

        cf) penicillin prophylaxis was of little benefit in preventing early -onset group B disease

      2. Intrapartum treatment of mothers found to be colonized near the time of delivery

        -> decreased neonatal colonization and early -onset sepsis

    • Recommendation for prophylaxis

      1. To use intrapartum antibiotics based on risk factors
      2. To obtain routine culture in women beginning at 36weeks and to treat those with a positive culture at the time of labor with penicillin G

      C. Listeriosis

    • Uncommon but probably underdiagnosed cause of neonatal sepsis
      G(+)aerobic motile bacillus that can be isolated from soil , water, and sewage
    • 1-5%of adults have listeria in their feces
    • Pregnant woman is susceptible because cell-mediated immunity is decreased
    • During pregnancy : may be asymptomatic or cause a febrile illness that is confused for
      influenza, pyelonephritis or meningitis
    • Diagnosis : apparent when blood cultures are positive
    • Meconium passage is common with fetal infection
    • Maternal listeria ; cause fetal infection that characteristically produces disseminated granulomatous lesions with microabscess
    • The neonate is particularly susceptible to infection and the mortality rate approach 50%

      : maternal antimicrobial treatment may be effective for fetal infection
    • Treatment: combination of ampicillin and gentamicin

      D. Salmonella and Shigella infection

      1. Salmonellosis

    • Fecal-borne illness
    • Symptoms: diarrhea, abdominal pain, fever, chills , nausea, vomiting
    • When pregnant women is infected ,amnionic fluid culture may be positive and infection can cause fetal death
    • Management :

      1. Rehydration
      2. Antimicrobials prolong the carrier state and are not given in uncomplicated infection

      2. Typhoid fever

    • Salmonella typhi is spread by oral ingestion of contaminated food, water, or milk
    • More likely to be encounted in pregnant woman or in those who are HIV infected

      ⑴ Pregnancy complicated by typhoid fever

      ① Abortion or preterm labor : 80%

      ② Fetal mortality : 60%

      ③ Maternal mortality : 25%

      ⑵ Treatment : chloramphenicol is the most effective treatment

      3. Shigellosis

    • Common cause of inflammatory exudative diarrhea in adults
    • Highly contagious with primary attack rates up to 75%, and exposed family members may be infected in over 50% of cases
    • Self limited
    • Treatment : trimethoprim- sulfomethoxazole

      E. Lyme disease

    • Caused by the spirochete Borrelia burgdorferi

    • Most commonly reported vector borne illness in the united states

    • Result from the bite of ticks of the gennus Ixodes

      early local infection : erythema migrans

    • Multisystemic involvement : skin lesions, arthralgia, and myalgia, carditis, and meningitis

    • Treatment : doxycycline or ampicllin

      for pregnant women ; oral amoxicillin or penicillin for 3 weeks

    • Neonatal infection: not associated with fetal death ,preterm delivery, or malformation

      III. Protozoal Infection

      A. Toxoplasmosis

    • Transmitted through encysted organisms by eating infected raw or undercooked meat and through contact with ooctyes in infected cat feces

    • Can be acquired congenitally by transplacental transfer

    • Fatigue ,muscle pains and sometimes lympadenopathy,but most often infection is subclinical

    • Infection in pregnancy : may cause abortion or result in a live - born infant with evidence of disease

    • 1-5/1000 pregnancies

    • The risk of fetal infection increased with duration of pregnancy (over all 50%)

    • The virulence of fetal infection is greater the earlier that infection is acquired

      : Fortunately infection is less common earlier in pregnancy

    • Less than 1/4 of newborns with congenital toxoplasmosis have signs of clinical illness at birth : low birth weight, hepatosplenomegaly, icterus, and anemia, neurologic disease with convulsion, intracranial calcification, mental retardation, and hydrocephaly or microcephaly, chorioretinitis

      1. Preconceptional serological screening

      ① If anti-toxoplasma Ig -G antibody is confirmed before pregnancy

      ? ? : the woman is not at risk for congenitally infected fetus

      ② If antibody is present in low titers

      ? ? probably represents previously acquired immunity

      ③ Accurate confirmation of active infection

      ? ? rise in Ig-G titer ,greater than 1:512

      ④ If titer greater 1: 256

      ? ? : increased microcephaly, deafness, and mental retardation

      2. Management

      Spiromycin : for the active disease

      reduce the incidence of fetal infection

      B. Malaria

    • Four species of plasmodium: vivax, ovale, malarie, and falciparum

      ->transmitted by the bite of a female Anopheles mosquito

    • Characterized by fever and flu-like symptoms including chills, headache myalgia and malaise which may occur at intervals

      1. Effect on pregnancy

    • The incidence of abortion and preterm labor is increased
    • Increased fetal loss : related to placental and fetal infection

      -> Parasite have on affinity for decidual vessels and may involve the placenta
    • Congenital malaria :7% of neonate in nonimmune women

      2. Treatment

    • Commonly used antimalarial drugs are not contraindicate during pregnancy

      1. Chloroquine : the treatment of choice
      2. Quinidine : to treat critically ill persons infected with falciparum malaria
      3. Mefloquine: choloroquine -resistant infections

      3. Prophylaxis

    • Chloroquine 300mg of base given orally once a week in initiated 1 to 2 weeks before the endemic area is entered, and this is continued until 4weeks after return to non endemic areas

      C. Amebiasis

    • Amoebic dysentery may take a fulminant course during pregnancy
    • If complicated by a hepatic abscess : prognosis is worse
    • Metronidazole is the drug of choice