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3.

07 Infectious Diseases and Sexually Transmitted Infections


Marth Louie Z. Tarroza, M.D |November 19, 2018

I. Introduction to Infectious Disease FETAL AND NEWBORN IMMUNOLOGY
A. Terminologies • Fetal cell-mediated and humoral immunity (starts to develop at 9-15
B. Maternal and Fetal Immunology weeks AOG)
II. Viral Infections
• IgM:
A. Cytomegalovirus
B. Varicella – Zoster o Primary fetal response to infection
C. Influenza • IgG:
D. Mumps o Passive immunity transferred across the placenta
E. Measles o Transfer rise starting 16 weeks AOG
F. Rubella
G. Parvovirus o By 26 weeks level of IgG fetal = mother
H. Zika • Breastfeeding:
III. Bacterial Infections o Protective against infection but begins to decline at 2 months of
A. Group A Streptococcus age
B. Group B Streptococcus
C. Methicillin-Resistant Staphylococcus aureus
D. Listeriosis II. VIRAL INFECTIONS
IV. Protozoal Infections A. CYTOMEGALOVIRUS
A. Toxoplasmosis • DNA Herpes Virus
B. Malaria
C. Amebiasis • Most common perinatal infection in developed countries
V. Sexually Transmitted Diseases • Secreted into all bodily fluids
A. Syphilis • Transmission:
B. Gonorrhea o Person-to-person
C. Chlamydia
D. Herpes Simplex Virus o Transplacental
E. Chancroid o At delivery
F. Human Papilloma Virus o Breastfeeding
G. Vaginitis
i. Bacterial Vaginosis
MATERNAL
ii. Trichomoniasis
iii. Candidiasis • Greatest risk: women who are seronegative before pregnancy but
H. Human Immunodeficiency Virus who develop primary CMV during pregnancy
VI. References o 30-36% in the 1st trimester
VII. Quiz
o 34-40% in the 2nd trimester
o 40-72% in the 3rd trimester (UHighest risk)
No objectives were given by the lecturer. L
• Most are ASYMPTOMATIC
• 10-15% have mononucleosis-like syndrome (which includes fever,
Legend:
pharyngitis, lymphadenopathy and polyarthritis)
Supplementary Emphasized
Audio Recording • Immunocompromised patients - myocarditis, pneumonitis, hepatitis,
Book Information Notes
retinitis, gastroenteritis, or meningoencephalitis
& U ❤
FETAL

I. INTRODUCTION TO INFECTIOUS DISEASE • Symptomatic CMV Infection
A. Terminologies o Newborns with apparent sequelae of in-utero-acquired CMV
Horizontal Transmission infection
• Spread of an infectious agent from one individual to another o Syndrome- growth restriction, microcephaly, intracranial
calcifications, chorioretinitis, mental and motor retardation,
Vertical Transmission sensorineural deficits, hepatosplenomegaly, jaundice, hemolytic
• Passage from the mother to her fetus of an infectious agent through anemia, and thrombocytopenic purpura
placenta, during labor or delivery or by breast feeding

Secondary Attack Rate
• Probability that infection develops in a susceptible individual
following known contact with an infectious person

B. Maternal and Fetal Immunology
MATERNAL
• ↑ CD4+ T cells that secrete Th2-type cytokines (interleukins): Th2 bias
• ↓ Th1-type cytokine production (interferon gamma and interleukin 2)
U This affects, the ability to rapidly eliminate certain intracellular
pathogens during pregnancy Figure 1. CMV Infection (from ppt)
U figure showing intracranial calcification


TRANSCRIBERS Sese, Silva, Silverio, Sison, So EDITOR of
♡Pam Puno 09288929910 1 12
DIAGNOSIS o Contagious from day 1 before the onset of the rash until the
• Routine prenatal CMV serologic screening is currently NOT lesions become crusted
recommended U Acquired predominantly during childhood and almost 90% of
• GOLD STANDARD: CMV Nucleic Acid Amplification Testing adults have serologic evidence of immunity
(NAAT) of amnionic fluid

• Primary Infection
o CMV-specific IgG testing of paired acute and convalescent sera
o CMV IgM - does NOT accurately reflect timing of seroconversion
because it is usually:
§ Elevated for more than a year
§ Found in reactivation or reinfection with a new strain of CMV
o CMV IgG avidity testing - ↑ anti-CMV IgG level indicates primary
maternal infection >6 months before testing

Figure 3. VZV Infection (from ppt)


MATERNAL
• Mortality is predominantly due to VZV Pneumonia
o Risk Factors:
§ Smoking
§ >100 cutaneous lesions
o Symptoms usually appear 3-5 days into the course of illness
o Fever, tachypnea, dry cough, dyspnea, and pleuritic pain
• Herpes Zoster/Shingles
o Reactivation of primary varicella
o Unilateral dermatomal vesicular eruption with severe pain

FETAL/NEONATAL
Congenital Varicella Syndrome- rare
Chorioretinitis Hydronephrosis
Microphthalmia Limb hypoplasia
Cerebral Cortical Atrophy Cicatricial skin lesions
Growth restriction

• Highest risk for Congenital Varicella syndrome: between 13-20


weeks U After 20 weeks, researchers found that there is no
clinical evidence of congenital infection
• If the fetus/neonate is exposed to active infection before or during
Figure 2. Algorithm for evaluation of suspected maternal primary delivery, before maternal antibody has been formed
CMV infection in pregnancy. Note: In Doc’s ppt, abnormal maternal o Fetus has a higher risk of disseminated visceral and CNS
CMV screening: CMV IgG (+), CMV IgM (+) is placed instead of disease (commonly fatal)
suspected maternal CMV infection. U After getting the CMV IgG and
IgM, we will use the IgG avidity testing to confirm if the CMV infection
is the latent or primary CMV infection ❤

MANAGEMENT AND PREVENTION


• Limited to SYMPTOMATIC TREATMENT
• If recent primary infection is confirmed, amnionic fluid analysis
should be offered.
• There is NO proven treatment available for CMV infection
• There is also currently NO CMV vaccine available

Figure 4. Atrophy of the lower extremity with bony defects and


B. VARICELLA-ZOSTER VIRUS
scarring in a fetus infected during the first trimester by varicella (ppt)
• Double-stranded DNA herpes virus
• Primary Infection - Varicella or Chickenpox
DIAGNOSIS
o Direct contact and/or Respiratory transmission
• Usually diagnosed clinically
• Incubation period: 10-21 days
• Confirmed by NAAT of vesicular fluid
o 1 to 2-day flu-like prodrome
o Pruritic vesicular lesions that crust after 3-7 days • Tzanck smear; tissue culture or direct fluorescent antibody testing


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MANAGEMENT o Oseltamivir (Tamiflu) - orally for treatment and
• Maternal Viral Exposure chemoprophylaxis
o With negative history - VZV Serologic Testing o Zanamivir (Relenza) - inhaled
§ Seronegative - given Varicella Zoster Immunoglobulin o Peramivir (Rapivad) - IV
(VariZIG) • Adamantanes
- Best given within 96 hours of exposure o Amantadine and Rimantadine - treatment and prophylaxis
- Approved for up to 10 days of exposure • Vaccines
o With known history of Varicella o Formulated annually
§ VariZIG is not indicated o Optimally given in October to November
o Should be isolated from other pregnant patients o No teratogenicity or other adverse maternal or fetal events
o Chest radiograph (with abdominal shield) is recommended
o Most patients only require supportive care, but those who D. MUMPS VIRUS
require IV and especially those with pneumonia are admitted • RNA Paramyxoviridae
o IV Acyclovir Therapy - 500mg/m2 or 10-15mg/kg every 8hrs • Infects the salivary glands, gonads, meninges, pancreas, and other
organs
• Fetal/Neonatal Infection
o Varicella-Zoster Immune Globulin (VZIG)
§ Neonates born to mothers who have clinical evidence of
varicella 5 days before and up to 2 days after delivery
should be given VZIG
o Vaccination
§ Not recommended for pregnant women or for those who
may become pregnant within a month following each
vaccine dose
§ The vaccine is an Attenuated live-vaccine Figure 6. Mumps Virus (from ppt)
- Non-pregnant adolescents and adults with no history of
varicella TRANSMISSION
- Two doses of Varivax given 4 to 8 weeks apart • Direct contact with respiratory secretions, saliva
• Fomites
C. INFLUENZA VIRUS
• Influenza A and B form one genus of RNA viruses which cause MATERNAL AND FETAL
epidemic human disease • Women who develop mumps in their 1st trimester may have greater
• Influenza A viruses are subclassified further by hemagglutinin (H) risk of spontaneous abortion
and neuraminidase (N) surface antigens • Not associated with congenital malformations
• Fetal infection is RARE

MANAGEMENT AND PREVENTION


• Treatment is symptomatic
• Mumps during pregnancy is no more severe than in non-pregnant
adults
• MMR is contraindicated in pregnancy

E. MEASLES VIRUS
• RNA Paramyxoviridae
• Highly infectious
• Fever, coryza, conjunctivitis, and cough (Note the 3C’s in measles ♡)
Figure 5. Structure of influenza Virus (from ppt) • Erythematous maculopapular rash develops on the face and neck
à back, trunk, and extremities
• Koplik spots
MATERNAL AND FETAL
• Fever, dry cough, and systemic symptoms
• Pregnant women appear to be more susceptible to serious
complications, particularly pulmonary involvement (maternal
mortality rate ~1%)
• No firm evidence links Influenza A and congenital malformations

MANAGEMENT
• Neuraminidase inhibitors
o Highly effective
Figure 7. Measles Virus Rash and Koplik’s spots U small, white
o Category C, thus used when potential benefits outweigh risks
lesions with surrounding erythema in the oral cavity (from ppt)


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MATERNAL AND FETAL
• Not appear to be teratogenic
• ↑ rate of spontaneous abortion, preterm delivery and LBW neonates

DIAGNOSIS
• IgM Antibodies
• RT-PCR tests

MANAGEMENT AND PREVENTION


• Treatment is supportive
• Pregnant women without evidence of measles immunity - Immune
globulin 400mg/kg IV
• Active vaccination is NOT performed during pregnancy
• Susceptible women can be vaccinated postpartum Figure 9. Illustration of the Congenital Rubella Syndrome. (from ppt)
U Vaccination is not contraindicated with breastfeeding
G. PARVOVIRUS
F. RUBELLA VIRUS • B19 virus, small single-stranded DNA virus
• RNA Togavirus • Replicates in rapidly proliferating cells such as Erythroblast
• “German measles” precursor
• Incubation period: 12-23 days • Causes “Erythema infectiosum or fifth disease”
o Viremia precedes clinical signs by about a week • Incubation period:
o Infectious during viremia and through 7 days after the rash o Infected person developed viremia 4 to 14 days after exposure
appears • Transmission:
• Transmission: nasopharyngeal secretions o Respiratory
o Hand to mouth contact
MATERNAL
• Mild febrile illness with a generalized maculopapular rash MATERNAL
o Starts on the face → trunk and extremities • 20-30% is asymptomatic
• Usual complains of arthralgias, arthritis, head and neck • Fever, headache, flu-like symptoms and symmetrical arthralgia
lymphadenopathy and conjunctivitis • Bright red rash with erythroderma affects the face called “slapped
• 25-50% of infections are asymptomatic cheek appearance”
• Several days after IgM is produced, IgG antibody is detectable and
persists for life with natural immunity

Figure 8. Maculopapular rash from Rubella virus, starts in the face


and spreads to the trunk and extremities.

FETAL
Figure 10. (L) Characteristic slapped cheek appearance from
• Infection in the first trimester poses significant risk for abortion and
Parvovirus. (R) Hydrops fetalis from Parvovirus B19 infection. (ppt)
severe congenital malformations
• Worst during organogenesis
FETAL
o 1st 12 weeks: 90% risk of having congenital malformations
o 13 – 14th weeks: 50% risk • Vertical transmission to the fetus is up to a third of maternal
o End of 2nd trimester: 25% risk parvovirus infections
• Associated with abortion, stillbirth and non-immune hydrops
o Rate of fetal loss:
Congenital Rubella Syndrome
§ 8-17% before 20 weeks
Cardiac septal defects Hepatosplenomegaly
§ 2-6% after midpregnancy
Pulmonary stenosis Sensorineural deafness
o Hydrops – 1% of fetuses of women with parvovirus
Microcephaly Intellectual disability § Critical period: 13-16 weeks gestation (time when fetal
Cataracts Neonatal purpura hepatic hemopoiesis is usually developed)
Microphthalmia Radiolucent bone disease


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DIAGNOSIS AND MANAGEMENT REVIEW: VIRAL INFECTIONS
• Maternal serologic testing for specific IgG and IgM antibodies 1. What is the gold standard in diagnosing CMV infection?
• Fetal infection: detection of B19 viral DNA in amniotic fluid or IgM • CMV NAAT of amnionic fluid
antibodies in fetal serum obtained by cordocentesis 2. When is the highest risk for congenital varicella
• Serial sonography is done every 2 weeks in women with recent syndrome?
infection U because based on a study, most parvovirus associated • Between 13-20 weeks
hydrops develop in the 1st 10 weeks after infection 3. Women who develops mumps in ___ trimester have a
• No parvovirus vaccine available greater risk of spontaneous abortion?
• No evidences suggests that antiviral treatments prevents maternal • 1st
or fetal infection 4. What is the management given for pregnant women
without evidence of measles immunity?
H. ZIKA VIRUS • Immune globulin 400mg/kg IV
• RNA virus of the Flaviviridae family 5. By how many weeks does the level of IgG in fetus
• Transmission: equals that of the mother?
o Mosquito bite • 26 weeks
§ 1st major mosquito-borne teratogen
o Sexual transmission
III. BACTERIAL INFECTIONS
MATERNAL A. GROUP A Streptococcus
• May be asymptomatic or cause mild symptoms of rash, fever, Streptococcus pyogenes
headache, arthralgia and conjunctivitis • Most common cause of severe maternal postpartum infection and
• Virus is typically detectable in blood around the time of symptom death worldwide
onset and may persist days to months in pregnant women • Produces numerous toxins and enzymes
• Guillain-Barre Syndrome may develop following infection o Pyrogenic exotoxin-producing strains
§ Usually associated with severe disease
FETAL
• Can be severely infected whether or not the mother is symptomatic • Streptococcal Toxic Shock Syndrome
o Presents with hypotension, fever, and evidence of multiorgan
• Fetal mortality – 7%
failure with associated bacteremia
• Fetal birth defects
o 5% - possible Zika infection
o 15% - laboratory confirmed infection in the 1st trimester • TREATMENT
o Clindamycin + Penicillin therapy
o Often with surgical debridement
Congenital Zika Syndrome
Microcephaly Intracranial calcifications B. GROUP B Streptococcus
Lissencephaly Ocular abnormalities Streptococcus agalactiae
Ventriculomegaly Congenital contractures
• Colonize the GI and GUT in 10-25% of pregnant women
• Spectrum of maternal and fetal GBS effects ranges from
asymptomatic colonization to septicemia

MATERNAL AND PERINATAL INFECTION


• Implicated in adverse pregnancy outcomes that include preterm
labor, prematurely ruptured membranes, clinical and subclinical
chorioamnionitis and fetal infections
• Can also cause maternal bacteriuria, pyelonephritis, osteomyelitis,
post-partum mastitis and puerperal infections
• Leading infectious cause of morbidity and mortality among infants
in US
• Early-onset Disease:
o Infection occurs <7 days after birth
§ Septicemia involves signs of serious illness that usually
develop within 6-12 hours of birth
Figure 11. Congenital Zika Syndrome (from ppt) -Babies are observed with respiratory distress, apnea,
hypotension
DIAGNOSIS AND MANAGEMENT • Late-onset Disease:
• Detection of ZIKA virus RNA in blood or urine by serological testing o Manifests as meningitis 1 week to 3 months after birth
by PCR o Mortality rate, although appreciable, is less compared with early-
• No specific treatment or vaccine is available but several vaccine onset sepsis
candidates are in development


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Skin and soft tissue infection
• Most common presentation of MRSA pregnant women (mastitis,
breast abscesses, perineal abscesses, infections at sites such as
abdominal and episiotomy incisions)
• Uncomplicated superficial infections – managed with drainage
and local wound care
• Severe superficial infections – MRSA-appropriate antibiotics are
given

ANTIBIOTICS
• Trimethoprim-sulfamethoxazole and Clindamycin
• Rifampin – not to be used for monotherapy
• Linezolid
• Doxycycline, Minocycline, and Tetracycline – not be used during
pregnancy Ubecause it is category C
• Vancomycin – 1st line therapy for inpatient serious MRSA infections
• For women with culture proven CA-MRSA infection during
pregnancy, we add single-dose Vancomycin to routine beta-lactam
perioperative prophylaxis for CS deliveries and higher-order
perineal lacerations

D. LISTERIOSIS
Listeria monocytogenes
Figure 12. Indications for intrapartum prophylaxis to prevent perinatal • Facultative intracellular gram (+) bacillus
group B streptococcal (GBS) disease under a universal prenatal • Nearly all cases are food borne
screening strategy based on combined vaginal and rectal cultures • More common in pregnant, immunocompromised, and the very old
obtained at 35 to 37 weeks’ gestation. ❤ or young

Table 1. Regimens for Intrapartum Antimicrobial Prophylaxis for MATERNAL AND FETAL INFECTION
Perinatal GBS Disease lifted from CDC 2010. • May be asymptomatic or cause febrile illness
REGIMEN TREATMENT • Maternal Listeriosis
Recommended Penicillin G, 5 million units IV o Causes fetal infection that characteristically produces
initial dose, then 2.5 to 3.0 disseminated granulomatous lesions with microabscesses
million units IV every 4 hours o Chorioamnionitis is common
until delivery o Placental lesions include multiple, well-demarcated
Alternative Ampicillin, 2 g IV initial dose, macroabscesses
then 1g IV every 4 hours or 2 g
every 6 hours until delivery MANAGEMENT
Penicillin allergy • Ampicillin + Gentamicin – recommended
• Patients not at high risk for • Cefazolin, 2 g IV initial dose, • Trimethoprim-sulfamethoxazole – penicillin-allergic women
anaphylaxis then 1 g IV every 8 hours until • No vaccine is available
delivery • Prevention: washing raw vegetables and cooking all raw food
• Patients at high risk for • Clindamycin, 900 mg IV
anaphylaxis and with GBS every 8 hours until delivery IV. PROTOZOAL INFECTIONS
susceptible to Clindamycin A. TOXOPLASMOSIS
• Patients at high risk for • Vancomycin, 1g IV every 12 • Caused by Toxoplasma gondii
anaphylaxis and with GBS hours until delivery o Obligate intracellular parasite
resistant to clindamycin or o Has a life cycle with 2 distinct stages:
susceptibility unknown § Feline Stage – takes place in the cat (definitive host) & its prey
§ Nonfeline Stage – tissue cysts containing bradyzoites or
C. METHICILLIN RESISTANT Staphylococcus aureus oocysts are ingested by intermediate host, including humans.
Staphylococcus aureus - Gastric acid digests the cysts to release the bradyzoites,
• Pyogenic gram (+) organism which infect the small intestinal epithelium
• Primarily colonizes the nares, skin, genital tissues and oropharynx - Tachyzoites infect all cells within the host mammal
o Human infection is acquired by eating raw or undercooked
• Community-acquired MRSA (CA-MRSA)
o Diagnosed in an outpatient setting or within 48 hours of meat infected with tissue cysts or by contact with oocysts from
cat feces
hospitalization in a person without traditional risk factors
• Hospital-associated MRSA (HA-MRSA)
o Nosocomial U usually for patients admitted >48 hours


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MATERNAL MATERNAL
• Include: fatigue, fever, headache, muscle pain, and sometimes, a • Fever, chills, and flu-like symptoms
maculopapular rash and posterior lymphadenopathy • May be associated with anemia and jaundice
• Associated with a 4x increased preterm delivery rate • P. falciparum infections may cause kidney failure, coma, and death
• Higher rates of perinatal morbidity and mortality
FETAL
• Most infected fetus are born without obvious stigmata of FETAL
toxoplasmosis • Adverse outcome includes stillbirth, preterm birth, and LBW
• Usually have generalized diseases expressed as LBW, • P. falciparum infection is the worst à spontaneous abortion
hepatosplenomegaly, jaundice, and anemia
• CLASSIC TRIAD (Note: CHI-TOxoplasmosis) DIAGNOSIS
o Chorioretinitis • Gold standard: Identification of parasites by microscopical
o Hydrocephalus evaluation of thick and thin blood smear
o Intracranial Calcifications
TREATMENT
Congenital Toxoplasmosis is suspected when sonography shows: • Uncomplicated malaria caused by P. vivax, P. malariae, P. ovale,
Hydrocephaly Placental thickening and chloroquine-sensitive P. falciparum
Intracranial/ Hepatic calcification Hyperechoic bowel o Chloroquine
Ascites Growth restriction o Hydroxychloroquine
• Multi-drug resistant P. falciparum
o Artesunate + Mefloquine
DIAGNOSIS
o Artesunate + Dihydroartemisinin-piperaquine
• IgG and IgM antibodies
o Artemether-lumefantrine
• Prenatal diagnosis performed using PCR amplification of
Toxoplasma DNA in amniotic fluid
PREVENTION AND CHEMOPROPHYLAXIS
o Sensitivity of PCR varies with gestational age and is lowest
• Vector Control:
before 18 weeks
o Insecticide-treated netting
o Pyrethroid insecticides
MANAGEMENT
o DEET-based insect repellant
• Spiramycin – cannot be used in treating fetal infection because it
• Chemoprophylaxis: Chloroquine and Hydroxychloroquine
cannot cross the placenta
• Pyrimethamine-sulfonamide + Folinic acid – for selected C. AMEBIASIS
maternal infection after 18 weeks or suspected fetal infection
• Caused by Entamoeba histolytica
• Manifestation: fever, abdominal pain, and bloody stools
PREVENTION
• Cooking meat to safe temperature DIAGNOSIS
• Peeling or thoroughly washing fruits and vegetables
• Stool Examination: (+) E. histolytica cysts or trophozoites
• Cleaning all food preparation surfaces and utensils
• Wearing gloves when changing cat litter TREATMENT
• Avoid feeding cats with raw or undercooked meat and keeping cat
• Metronidazole
indoors
• Tinidazole
B. MALARIA
V. SEXUALLY TRANSMITTED INFECTIONS
• Transmitted by infected Anopheles mosquitos
A. Syphilis
• Caused by 6 species of Plasmodium:
• Caused by Treponema pallidum
o P. falciparum
o Spirochete
o P. vivax
o Replicate and disseminate through lymphatic channels
o 2 species of P. ovale
o Incubation period: 3-4 weeks
o P. malariae
o Readily crosses the placenta to cause congenital infection
o P. knowlesi
Stages and Manifestation
• Primary Syphilis
o Chancre
§ Solitary, painless lesion with raised firm border and a red
smooth ulcerated base without significant pus
§ Resolve spontaneously in 2-8 weeks, even if untreated
o Non-suppurative lymphadenopathy
Figure 13. Female Anopheles Mosquito.


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Figure 14. Primary Syphilis. Chancre with a raised, firm border, and Figure 16. Congenital Syphilis. (A) Fetogram of a stillborn infant infected
smooth, red base. & (photo not from ppt) with syphilis showing the “moth-eaten” appearance of the femur. (B)
Enlarged hydropic placenta of a syphilis-infected neonate. (from ppt)
• Secondary Syphilis U Note the large and paler placenta
o Dissemination of spirochetes to affect multiple organ
o 4-10 weeks after the appearance of chancre DIAGNOSIS
o Diffuse macular rash, plantar and palmar target-like lesions, • Screening is performed at the first prenatal visit
patchy alopecia, and mucous patches • Non-Treponemal Testing
o Condylomata lata Ufresh-colored papules and nodules found o Venereal Disease Research Laboratory (VDRL) & Rapid
on perineum and perianal area Plasma Reagin (RPR)
o Highly infectious stage of syphillis § Both tests measure patient IgM and IgG antibodies formed
against cardiolipin that is released from damaged host cells
§ False (+) results – also ↑ in IV drug abuse, SLE, aging,
leprosy, and cancer
§ False (-) results – women with very early primary syphilis
(seroconversion occurs in 3-6 weeks)
§ With (+) results – findings are quantified and expressed as
titers
§ Following treatment, serologic testing is repeated at 3-6
months which usually confirms a four-fold ↓ in VDRL or RPR
titers
• Treponemal Specific
Figure 15. Secondary Syphilis. (L) Target lesions on the palms of a o Fluorescent Treponemal-Antibody Absorption Tests (FTA-
pregnant woman. (R) Mucous patches around the mouth of a pregnant ABS) and T. pallidum Passive Particle Agglutination (TP-
woman. & (photo not from ppt) PA) Test
§ The antibodies detected appear up to few weeks earlier than
• Latent Syphilis those detected with non-treponemal testing
o Develops when primary or secondary syphilis is not treated but
MANAGEMENT
clinical manifestations still resolve (asymptomatic)
o Early Latent – Uclinical disease acquired within the preceding • Following maternal diagnosis, sonographic evaluation is performed
12 months for fetuses >20 weeks’ gestation U the ff are the red flags:
o Late Latent- Udisease diagnosed by 12 months can either be o Hepatomegaly
late latent or latent syphilis of unknown duration o Placental Thickening
o Latent syphilis of unknown duration o Hydramnios
o Ascites
• Tertiary Syphilis o Hydrops fetalis
o Slowly progressive disease affecting any organ system o ↑ middle cerebral artery doppler velocimetry
o Rarely seen in reproductive aged women • For fetuses of viable age with sonographic findings, antepartum
FHR monitoring prior to treatment is recommended.
CONGENITAL SYPHILIS o Spontaneous late decelerations or a non-reactive tracing
reflects an extremely ill fetus that may poorly tolerate a Jarisch-
• Maternal infection can lead to preterm labor, fetal death, fetal
Herxeimer Reaction
growth restriction or fetal infection
• Jarisch-Herxheimer Reaction – a reaction following a
• Jaundice with petechiae or purpuric skin lesions, lymphadenopathy,
Penicillin treatment
rhinitis, pneumonia, myocarditis, nephrosis or long-bone
§ Uterine contractions, mild maternal temperature elevation,
involvement
• Placenta ↓ fetal movement, FHR deceleration
o Grossly: large and pale § Supportive Treatment: antipyretics, hydration and oxygen
o Microscopically: villi loses their characteristic arborization and supplementation
become thicker and clubbed & Parenteral Penicillin G remains the preferred treatment for
all stages of syphilis during pregnancy


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Table 2. Recommended Treatment for Pregnant Women with Syphilis Gonococcal Ceftriaxone 1-2g IV every 12hrs for at
CATEGORY TREATMENT Endocarditis least 4 weeks + Azithromycin 1g orally
Early syphilis Benzathine Penicillin G, Gonococcal Ceftriaxone 1-2g IV every 12hrs for 10-
2.4 million units IM as a single Meningitis 14 days + Azithromycin 1g orally
injection- some recommend a 2nd
dose 1 week later C. CHLAMYDIA
> 1 year duration Benzathine Penicillin G, 2.4 million • Most common STD
units IM weekly for 3 doses • Etiology: C. trachomatis
Neurosyphilis Aqueous crystalline penicillin G, • Most pregnant women are asymptomatic
3-4 million units IV every 4 hours o But 1/3 have urethral syndrome, urethritis or Bartholin gland
for 10-14 days, or infection
Aqueous procaine penicillin, 2.4 • Clinical presentation: Mucopurulent cervical discharge
million units IM daily, plus • Can have deleterious effects in any trimester
probenecid 500 mg orally 4 times o Preterm delivery
daily, both for 10-14 days. o PROM
o Postpartum infection
B. Gonorrhea o Neonatal infection (e.g. conjunctivitis, neonatal pneumonia)
• 2nd most common cause of STD (Note: #1 is Chlamydia)
• Etiology: N. gonorrhea DIAGNOSIS
• Infection is usually limited to lower genital tract (&includes cervix, • Culture or NAAT of cervix, urethral glands, and urine
urethra, periurethral and vestibular glands)
Table 5. Treatment of Chlamydia trachomatis Infections During
• Can have deleterious effects in any trimester
o Septic abortion Pregnancy
o Preterm delivery REGIMEN TREATMENT
o PROM Preferred choice • Azithromycin 1000mg (1g) orally as
o Chorioamnionitis a single dose, or
• Amoxicillin 500mg oral, 3x daily for
o Postpartum infection
7 days
U Vertical transmission predominantly due to contact with vaginal Alternatives • Erythromycin base, 500mg orally,
infection after birth 4x daily over 7 days, or
o Babies with infected mothers can have gonococcal • Erythromycin ethylsuccinate,
ophthalmia neonatorum à corneal scarring, ocular 800mg oral, 4x daily over 7 days, or
perforations, and blindness as complications • Erythromycin base, 250 mg orally
4x daily for 14 days, or
DIAGNOSIS • Erythromycin ethylsuccinate, 400
mg orally 4x daily for 14 days
• Vaginal discharge, cervix and urine
o Culture, or LYMPHOGRANULOMA VENEREUM
o Nucleic acid amplification tests (NAATs)
• Caused by L1, L2 and L3 serovars
• Inguinal adenitis may develop and this give rise to the “groove sign”
Table 3. Treatment of Uncomplicated Gonococcal Infection
• Fistula formation involving the rectum, perineum and vulva may
REGIMEN TREATMENT develop
Typical Regimen Ceftriaxone 250mg IM + Azithromycin • TREATMENT
1g orally; one dose only o Erythromycin base 500mg orally 4x a day for 21 days
U Azithromycin provides a different o Azithromycin 1g orally for 21 days
MOA against N. Gonorrhea and also
treats possible chlamydial infection
Alternative Regimen Cefixime 400mg oral + Azithromycin
1g oral; one dose
Cephalosporin Gentamicin 240mg IM +
allergy Azithromycin 2g oral; one dose only

Table 4. Treatment of Disseminated Gonococcal Infection.


U Infections can manifest as petechial or pustular lesions, arthralgia
Figure 17. LGV (photo not from ppt/book)
or septic arthritis
CATEGORY TREATMENT D. HERPES SIMPLEX VIRUS
Septic Arthritis Ceftriaxone 1g IV/IM every 24hrs + • HSV type 1
Azithromycin 1g orally o Responsible for most noncongenital infections
UThis can be continued for 24-48hrs o Typically acquired during childhood
after clinical improvement • HSV type 2
Then, therapy is shifted to oral agent to o Almost exclusively from the genital tract
complete a 1-week treatment course o Transmitted via sexual contact


3.07 INFECTIOUS DISEASES AND STIs 9 of
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CLINICAL MANIFESTATIONS • Postpartum (10%)
• First Episode Primary Infection o Uncommon
o HSV-1 or HSV-2 isolated from a lesion in the absence of their o Passed to the newborn by contact with an infected mother,
respective serological antibodies family member or healthcare worker
o Incubation period: 6-8 days o Clinical presentation- same with peripartum transmission
o After incubation, it is followed by papular eruption with itching
or tingling and may ulcerate • In-utero (5%)
o (+) inguinal adenopathy o Rare
o Transient systemic influenza-like symptoms are frequent o Part of TORCH infections (toxoplasma, other, rubella, CMV,
o All symptoms typically disappear after 2-4 weeks herpes virus)
o Classically involves:
§ Skin: blisters and scarring
§ CNS: hydranencephaly, microcephaly, intracranial
calcifications
§ Eyes: chorioretinitis, microphthalmia

DIAGNOSIS
• Direct virological test- specimen for mucocutaneous lesion
• PCR
• Culture

TREATMENT
Figure 18. First episode primary genital herpes simplex virus
infection. On the left labium majora and mons, both vesicles and Table 6. Antiviral Medications for Herpesvirus infection in pregnancy.
ulcers are seen. (photo from ppt) CATEGORY TREATMENT
Primary or 1st episode • Acyclovir 400mg oral 3x daily for
• First Episode Non-primary Infection infection 7-10 days, or
o One HSV type isolated from a lesion in a woman who has • Valacyclovir 1 g orally 2x a day
other HSV serological HSV-type antibody present for 7–10 days
o Fewer lesions, less pain, fewer systemic manifestations and Symptomatic recurrent • Acyclovir 400 mg orally 3x a day
briefer duration of lesions infection for 5 days, or
(episodic therapy) • Acyclovir 800 mg orally 2x a day
• Recurrent Disease for 5 days, or
o Isolation of HSV-1 or HSV-2 from the genital tract in women • Valacyclovir, 500 mg orally 2x a
with the same serotype antibodies day for 3 days, or
o Fewer lesions, less tender, and virus is shed for a shorter time
• Valacyclovir, 1 g orally once a
this is likely because of some immunity from cross-reacting
day for 5 days
antibodies U
Daily suppression • Acyclovir, 400 mg orally 3x a day
o Most frequent in the 1st year after initial infection
from 36 weeks until delivery, or
• Valacyclovir, 500 mg orally 2x a
• Asymptomatic Viral Shedding
day from 36 weeks until delivery
o No clinical findings
o Most women shed HSV virus intermittently over time and most
HSV transmission to a partner occurs during these periods Peripartum Shedding Prophylaxis
• CS delivery is indicated for women with active genital lesions or
prodromal symptoms
• Some studies have shown that Acyclovir or Valacyclovir
suppression initiated at 36 weeks’ gestation for gravidas with
recurrences in pregnancy lowers the number of HSV outbreaks at
term

E. CHANCROID
• Etiology: Haemophilus ducreyi
• “Soft chancre”
• Painful, non-indurated genital ulcers
Figure 19. HSV vesicles on an edematous, erythematous base. This • (+) Painful suppurative inguinal lymphadenopathy
will later form ulcers that dry, crust and heal (photo not from ppt/book)

VERTICAL TRANSMISSION OF HSV


• Peripartum (85%)
o Fetus is exposed to virus shed from cervix or lower genital tract
o HSV invades the uterus following membrane rupture or is
transmitted by contact at delivery
o Manifestations:
§ Localized skin, eye, mouth (SEM) disease (40%)
§ CNS disease with encephalitis (30%)
§ Disseminated disease with involvement of multiple major Figure 20. Chancroid in female genitalia. (photo not from ppt/book)
organs (32%)


3.07 INFECTIOUS DISEASES AND STIs 10 of
12
TREATMENT Cont… Bacterial Trichomoniasis Candidiasis
• Azithromycin 1g orally Vaginosis
• Erythromycin 500mg 3x a day for 7 days Signs/ Most are Yellow purulent Profuse,
• Ceftriaxone 250mg IM Symptoms asymptomatic, discharge, irritating
but typically Pruritus, discharge
F. HUMAN PAPILLOMAVIRUS (HPV) complain of foul Vulvovaginal
thin vaginal erythema,
• HPV types 6 and 11 discharge “Strawberry
o Causes mucocutaneous external genital warts termed cervix”
Condyloma acuminata
Diagnosis Amsel’s Criteria Wet smear - Curd-like
• HPV types 16 and 18 (3/4 needed) flagellated, discharge on
o Associated with dysplasia 1.Vaginal pH > motile organism examination
4.5
CONDYLOMA ACCUMINATA 2.Thin, milky, NAAT analysis Spaghetti and
• General wart eradication in pregnancy unless they are symptomatic non- Culture meatballs on
• Therapy is directed toward debulking the symptomatic warts yet inflammatory microscopy
minimizing toxicity to mother and fetus discharge
3.>20% clue
• TREATMENT cells
o Trichloro- or bichloroacetic acid 4.(+) whiff test*
o Cryotherapy, laser ablation, surgical excision Treatment • Metronidazole Metronidazole For
500mg/tab BID 2g as single asymptomatic,
for 7 days dose no treatment
• Metronidazole is needed
0.75% gel, one Metronidazole
applicator 500mg/tab, 1 Symptomatic:
vaginally for 5 tab twice a day Miconazole
days for 7 days Butoconazole
• Clindamycin Clotrimazole
2% cream, one Fluconazole-
applicator (non-pregnant)
intravaginally at
night for 7 days
Figure 21. Extensive external genital warts in a postpartum woman
Alternatives:
(photo from ppt)
• Clindamycin
300mg orally
VACCINATION
BID for 7 days
• Cervarix (HPV2)- Bivalent (16 and 18) • Clindamycin
• Gardasil (HPV4)- Quadrivalent (6, 11, 16, and 18) 100mg/ovules
• Gardasil 9 (HPV9)- Nonavalent (HPV4 + 31, 33, 45, 52, 58) intravaginally
• For ages 15-26: Give 3 doses at 0, 1-2, and 6mos for 3 days
• Ages 9-14: 2 doses at 0, and 6-12mos *NOTE: Whiff test- add several drops of 10% KOH to the vaginal
• Vaccines NOT recommended for pregnant patients discharge. A resulting fishy odor means a (+) result.

NEONATAL INFECTION H. HUMAN IMMUNODEFICIENCY VIRUS


• Vertical transmission rates are minimal • Caused by RNA retroviruses HIV-1 and HIV-2
• Juvenile-onset Recurrent Respiratory Papillomatosis (JoRRP) • Incubation period: 3-6 weeks
o Rare, benign neoplasm of the larynx • Common symptoms:
o Causes hoarseness and respiratory distress in children and • Fever • Pharyngitis
most often caused by HPV 6 or 11 • Fatigue • Myalgia
o The benefit of CS delivery to ↓ transmission risk is unknown, and • Rash • Nausea
thus it is currently not recommended solely to prevent HPV • Headache • Diarrhea
transmission • Lymphadenopathy

G. VAGINITIS TRANSMISSION
Table 7. Different causes of vaginitis • Transplacental
Bacterial Trichomoniasis Candidiasis • Vertical transmission
Vaginosis o More common with preterm births and prolonged ROM
Causative Maldistribution Trichomonas Candida § 20% before 36 weeks
agent of normal vaginalis albicans § 50% just before delivery
vaginal flora: § 30% intrapartum
o Breastfeeding has a 30-40% transmission rate
↓ Lactobacilli,
↑ anaerobes SCREENING
(Gardnerella, • HIV screening is included in a comprehensive set of antenatal tests
Prevotella, but it can be declined
Bacteroides,
etc.)


3.07 INFECTIOUS DISEASES AND STIs 11 of
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DIAGNOSTICS • CD4+ count should be monitored at
• Screening with ELISA the initial visit and every 3-6 months
• Confirm with Western Blot Intrapartum Care • If HIV RNA level >1000 copies/mL or
• Immunofluorescence assay (IFA) is unknown before labor or ROM, plan
• CD4+ count of <200/mm3 is also considered a definitive dx of AIDS CS delivery at 38 weeks’ gestation
• If HIV RNA level >1000 or is unknown
ANTEPARTUM CARE
but labor or ROM has ensued,
• Standard prenatal laboratory tests, (e.g. CBC, Serum creatinine, benefits of CS delivery are unclear
Bacteriuria screening)
and labor plans are individualized
• Plasma HIV RNA quantification (“viral load”) - CD4+ T-cell count,
antiretroviral resistance testing • If HIV RNA level < 1000 copies/mL,
• Liver enzymes vaginal delivery is permitted; CS
• HSV-1 & -2, CMV, toxoplasmosis, and Hep B and C testing delivery not routinely recommended
• Baseline Chest XRay • Stat IV ZDV if HIV RNA level >1000
• TB testing with PPD copies/mL near delivery or is
• Evaluation of the need for pneumococcal, Hep A, Hep B, Tdap, and unknown. Dosing is 2 mg/kg IV load
influenza vaccines over 1 hour, then 1 mg/kg/hr until
• Sonographic evaluation of gestational age
delivery; IV ZDV should begin 3 hrs
MANAGEMENT before scheduled CS delivery
• Those taking oral antepartum ART
U What’s important here is that the patient diagnosed with HIV
should be given an ART even before or during pregnancy and it should take this during labor with sips
should be continued postpartum. After which, doc read the of water
recommendations for intrapartum care J
REFERENCES
CLINICAL SCENARIO RECOMMENDATIONS
• Dr. Tarroza’s powerpoint
Taking ART and • Continue current medication if viral • Williams 24th edition
becomes pregnant suppression is adequate and patient
• Recordings
can tolerate
QUIZ
ART Naive • Initiate ART: combine 2 NRTIs with
1. Treatment for gonorrhea if there is cephalosporin allergy?
either a ritonavir-boosted PI or an a. Cefixime + Azithromycin
integrase inhibitor b. Gentamicin + Azithromycin
• Preferred NRTI dual combinations: c. Ceftriaxone + Azithromycin
-abacavir/lamivudine d. All of the above
-tenofivir disoproxil fumarate (TDF) 2. What stage of syphilis is characterized by diffuse macular rash,
plantar and palmar target like lesions, patchy alopecia, and
/emitricitabine
mucous patches?
-TDF/lamivudine a. Primary
If abacavir is used, HLA-B*5701 b. Secondary
testing is completed to identify c. Tertiary
potential hypersensitivity reaction d. Latent
• Preferred PI: atazanavir/ritonavir or 3. Which does not belong to the classic triad of toxoplasmosis?
darunavir/ritonavir a. Hydrocephalus
b. Rashes
• Preferred integrase inhibitor: c. Intracranial calcifications
raltegravir d. Chorioretinitis
Prior ART use but not • Initiate ART with regimen based on 4. Guillain Barre Syndrome is associated with?
currently prior therapy history and resistance a. Measles Virus
training b. HPV
c. HIV
Antepartum Care • See antepartum screening test (pp. d. Zika Virus
1249 &)
• ART should be initiated ASAP
• For those with HIV RNA levels >500- Answer key: B, B, B, D
1000 copies/mL, order HIV
antiretroviral drug-resistance testing
but do not delay ART initiation
awaiting results
• Repeat HIV/RNA levels 2-4 weeks
after initiating (or changing) ART
drugs; monthly until RNA levels are
undetectable; then at least every 3
months; and finally at 34-36 weeks’
gestation for delivery planning


3.07 INFECTIOUS DISEASES AND STIs 12 of
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