Download Ñongenital infections

STATE ESTABLISHMENT «DNEPROPETROVSK MEDICAL ACADEMY
OF MINISTRY OF HEALTH UKRAINE »
“Сonfirmed;”
at methodical meeting
of hospital pediatrics №1 department
Сhief of department
professor _____________V. A. Kondratyev
“______” _________________ 2013 y.
METHODICAL INSTRUCTIONS
FOR STUDENTS` SELF-WORK
WHILE PREPARING FOR PRACTICAL LESSONS
Educational discipline
module №
Substantial module №
Theme of the lesson
Course
Faculty
pediatrics
2
11
Сongenital infections (TORCH – infections)
5
medical
Dnepropetrovsk, 2013.
1. Urgency of the theme: Congenital infections (CI) are transmitted to a fetus in ante- and
intranatal periods. During the last decade, despite the progress in diagnostics and treatment of CI,
we can trace their growth. Infectious pathology is one of the leading causes of stillbirth and
perinatal death of babies. It leads to a necessity of profound studying of diagnostic methods,
treatment and prevention of CI.
2. Specific aims:
А. Student must know:
1. CI definition.
2. Aetiological structure of CI.
3. Basic pathogenetic stages of infectious process of CI’s development.
4. Clinical signs of CI.
5.Features of clinical symptoms at cytomegalovirus infections, toxoplasmosis, chlamydiosis,
mycoplasmosis, herpetic infections, rubella.
6. Features of clinical symptoms of CI depending upon the term of fetus’ infection.
7. Auxillary methods of CI diagnostics.
8. Methods of CI’ treatment depending on infectious agent.
9. CI prevention.
B. A student must have the abilities to:
1. Discover typical anamnestic data and clinical symptoms of CI.
2. Make a differential diagnosis between CI and other newborns’ diseases.
3. Make a differential diagnosis between separate forms of CI.
4. Make a plan of examining a sick person having CI.
5. Make a plan of treating a sick person having CI.
3. Tasks for student’s self-work to prepare for practical studies.
3.1. The list of basic terms, parameters, descriptions, which students must master
preparing for lessons.
1. CI
Term
Definition
Congenital infections
2. HSV
Herpes simplex virus
3. Blastopathies
Affection (infectious) in a blastogenesis stage.
As a rule it is concluded with miscarriage.
4. Embryopathy
Affection on a stage of embryogenesis. It is
ended with a forming of small and big
congenital defects.
5. Fetopathy
Affection on a stage of fetogenesis. More
frequent generalized affection with typical
symptoms for infectious agent.
6. TORCH
Congenital infections (cytomegalovirus,
herpetic, toxoplasmosis, listeriosis,
mycoplasmosis, rubella).
7. PCR(polymerase chain reaction)
Method of DNA/RNA diagnostics is a complete
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equivalent of cultural methods of agent’s
excretion.
8. Innate CMV
CMV – herpetic virus №5, antenatal
transplacental infection.
9. Children’s CMV contamination
> 90% - In an antenatal period
5% - in an intranatal period
1% - in a postnatal period
10. Opportunistic infection
Clinical manifestations are possible only in the
case of immunodeficiency.
11. Chlamydia
Representative of intermediate existence form.
3.2. Thereotical questions for the lesson:
1. CI definition.
2. CI frequency among other newborns’ diseases.
3. Etiological structure of CI.
4. Features of fetus’s inflammatory process depending on gestation term.
5. Channels of CI’s infection.
6. Features of fetus and newborns’ immunity.
7. Fetoplacental barrier influence on fetus infections.
8. Basic pathogenetic links of CI’s development.
9. General clinical symptoms which are typical for CI.
10. Clinical features of separate CI (cytomegalovirus infections, toxoplasmosis, chlamydiosis,
mycoplasmosis, herpetic infections, rubella and other). Meaning of additional investigations in
CI diagnostics. CI complications.
11. Possibilities of laboratory and instrumental diagnostics.
12. The principles of CI therapy.
13. Prevention of CI.
4.3 . Practical works (tasks) which are performed on occupation:
1 To collect complaints, case history and personal (life) history
2. To inspect the child consistently
3. To reveal early symptoms of congenital infections
4. To reveal the signs of the complications of congenital infections
5. To evaluate the condition of the child and available clinical symptoms.
6. To evaluate the results of the additional methods of investigation
7. To make the clinical diagnosis according to classification.
8. To make the treatment plan.
9. To make recommendations of dispensary supervision.
.
4. Maintenance of the subject:
Intrauterine Infection
A variety of agents that infect the mother during pregnancy, labor, and/or delivery can infect
the fetus or newborn and cause fetal loss or early neonatal death, multiorgan dysfunction, and/or
injury to the developing brain. The most important pathogens are cytomegalovirus (CMV),
Toxoplasma gondii, herpes simplex virus, Treponema pallidum, and rubella virus.
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Pathogenesis and Epidemiology of Infections of the Neonatal Infant
Infections are a frequent and important cause of morbidity and mortality in the neonatal
period. As many as 2% of fetuses are infected in utero, and up to 10% of infants have infections in
the 1st mo of life. Neonatal infections are unique for several reasons. (1) Infectious agents can be
transmitted from the mother to the fetus or newborn infant by diverse modes. (2) Newborn infants
are less capable of responding to infection because of one or more immunologic deficiencies. (3)
Coexisting conditions often complicate the diagnosis and management of neonatal infections. (4)
The clinical manifestations of newborn infections vary and include subclinical infection, mild to
severe manifestations of focal or systemic infection, and rarely, congenital malformations resulting
from infection in the 1st trimester. The timing of exposure, inoculum size, immune status, and
virulence of the etiologic agent influence the expression of disease in a fetus or newborn infant. (5)
Maternal infection that is the source of transplacental fetal infection is often undiagnosed during
pregnancy because the mother was either asymptomatic or had nonspecific signs and symptoms at
the time of acute infection. (6) A wide variety of etiologic agents infect the newborn, including
bacteria, viruses, fungi, protozoa, and mycoplasmas. (7) Finally, with advances in neonatal
intensive care, increasingly immature, very low birthweight (VLBW) newborns are surviving and
remain in the hospital for a longer time, an environment that puts them at ongoing high risk for
infection.
Pathogenesis of Intrauterine Infection.
Intrauterine infection is a result of clinical or subclinical maternal infection with a variety of
agents (e.g., cytomegalovirus [CMV], Treponema pallidum, Toxoplasma gondii, rubella virus,
varicella virus, parvovirus B19) and hematogenous transplanscental transmission to the fetus.
Transplacental infection may occur at any time during gestation, and signs and symptoms may be
present at birth or be delayed for months or years. Infection may result in early spontaneous
abortion, congenital malformation, intrauterine growth restriction, premature birth, stillbirth, acute
disease in the neonatal period, or asymptomatic persistent infection with sequelae later in life. In
some cases, no apparent effects are seen in the newborn infant.
The timing of infection during gestation affects the outcome. First trimester infection may
alter embryogenesis, with resulting congenital malformations (congenital rubella). Third trimester
infection often results in active infection at the time of delivery (toxoplasmosis, syphilis). Infections
that occur late in gestation may lead to a delay in clinical manifestations until some time after birth
(syphilis).
Maternal infection is a necessary prerequisite for transplacental infection. For some etiologic
agents, maternal immunity is effective and antibody is protective for the fetus (rubella). For other
agents, maternal antibody may ameliorate the outcome of infection or have no effect (CMV). Even
without maternal antibody, transplacental transmission of infection to a fetus is variable, and the
placenta often functions as an effective barrier.
Etiology of Fetal and Neonatal Infection
A number of agents may infect newborns in utero, intrapartum, or postpartum. Intrauterine
transplacental infections of significance to the fetus and/or newborn include syphilis, rubella, CMV,
toxoplasmosis, parvovirus B19, and varicella. Although HSV, HIV, hepatitis B virus (HBV),
hepatitis C virus, and tuberculosis (TB) can each result in transplacental infection, the most
common mode of transmission for these agents is intrapartum during labor and delivery with
passage through an infected birth canal (HIV, HSV, HBV) or postnatal from contact with an
infected mother or caretaker (TB).
Any microorganism inhabiting the genitourinary or lower gastrointestinal tract may cause
intrapartum and postpartum infection. The most common bacteria are GBS, enteric organisms,
gonococci, and chlamydiae. The more common viruses are CMV, HSV, and HIV.
Congenital pneumonia may be caused by CMV, rubella virus, and T. pallidum.
Microorganisms causing pneumonia acquired during labor and delivery include GBS, gram4
negative enteric aerobes, Listeria monocytogenes, genital Mycoplasma, Chlamydia trachomatis,
CMV, HSV, and Candida species.
Clinical Manifestations of Transplacental Intrauterine Infections
Infection with agents that cross the placenta (CMV, T. pallidum, T. gondii, rubella,
parvovirus B19, others) may be asymptomatic at birth or may cause a spectrum of disease ranging
from relatively mild symptoms to multisystem involvement with severe and life-threatening
complications. For some agents, disease is characterized by chronicity, recurrence, or both (in the
mother and infant), and the agent may cause ongoing injury. Clinical signs and symptoms do not
help make a specific etiologic diagnosis, but rather raise suspicion of an intrauterine infection and
help distinguish these infections from acute bacterial infections that occur during labor and delivery.
The following signs and symptoms are common to many of these agents: intrauterine growth
restriction, microcephaly or hydrocephalus, intracranial calcifications, chorioretinitis, cataracts,
myocarditis, pneumonia, hepatosplenomegaly, direct hyperbilirubinemia, anemia,
thrombocytopenia, hydrops fetalis, and skin manifestations, including petechiae, purpura, and
vesicles. Many of these agents cause late sequelae, even if the infant is asymptomatic at birth. These
adverse outcomes include sensorineural hearing loss, visual disturbances (including blindness),
seizures, and neurodevelopmental abnormalities.
Table -- Clinical Manifestations of Transplacental Infections
Manifestation
Pathogen
Intrauterine Growth
Restriction
CMV, Plasmodium, rubella, toxoplasmosis, Treponema pallidum,
Trypanosoma cruzi, VZV
Congenital Anatomic
Defects
Cataracts
Rubella
Heart defects
Rubella
Hydrocephalus
HSV, lymphocytic choriomeningitis virus, rubella, toxoplasmosis
Intracranial calcification
CMV, HIV, toxoplasmosis, T. cruzi
Limb hypoplasia
VZV
Microcephaly
CMV, HSV, rubella, toxoplasmosis
Microphthalmos
CMV, rubella, toxoplasmosis
Neonatal Organ Involvement
Anemia
CMV, parvovirus, Plasmodium, rubella, toxoplasmosis, T. cruzi, T.
pallidum
Carditis
Coxsackieviruses, rubella, T. cruzi
Encephalitis
CMV, enteroviruses, HSV, rubella, toxoplasmosis, T. cruzi, T.
pallidum
Hepatitis
CMV, enteroviruses, HSV
Hepatosplenomegaly
CMV, enteroviruses, HIV, HSV, Plasmodium, rubella, T. cruzi, T.
pallidum
Hydrops
Parvovirus, T. pallidum, toxoplasmosis
Lymphadenopathy
CMV, HIV, rubella, toxoplasmosis, T. pallidum
Osteitis
Rubella, T. pallidum
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Manifestation
Pathogen
Petechiae, purpura
CMV, enteroviruses, rubella, T. cruzi
Pneumonitis
CMV, enteroviruses, HSV, measles, rubella, toxoplasmosis, T.
pallidum, VZV
Retinitis
CMV, HSV, lymphocytic choriomeningitis virus, rubella,
toxoplasmosis, T. pallidum, West Nile virus
Rhinitis
Enteroviruses, T. pallidum
Skin lesions
Entroviruses, HSV, measles, rubella, T. pallidum, VZV
Thrombocytopenia
CMV, enteroviruses, HIV, HSV, rubella, toxoplasmosis, T. pallidum
Late Sequelae
Convulsions
CMV, enteroviruses, rubella, toxoplasmosis
Deafness
CMV, rubella, toxoplasmosis
Dental/skeletal
Rubella, T. pallidum
Endocrinopathies
Rubella, toxoplasmosis
Eye pathology
HSV, rubella, toxoplasmosis, T. cruzi, T. pallidum. VZV
Hepatitis
Hepatitis B
Mental retardation
CMV, HIV, HSV, rubella, toxoplasmosis, T. cruzi, VZV
Nephrotic syndrome
Plasmodium, T. pallidum
CMV = cytomegalovirus; VZV = varicella-zoster virus; HSV = herpes simplex virus.
SUSPECTED INTRAUTERINE INFECTION
The acronym TORCH refers to toxoplasmosis, other agents, (syphilis, etc.), rubella, CMV,
and HSV.
Although the term may be helpful in remembering some of the etiologic agents of
intrauterine infection, the TORCH battery of serologic tests has a poor diagnostic yield, and
appropriate diagnostic studies should be selected for each etiologic agent under consideration. CMV
and HSV require culture or polymerase chain reaction (PCR) methods, whereas syphilis,
toxoplasmosis, and rubella are diagnosed by specific serologic methods.
In most cases of suspected fetal infection, concern is not raised until the pregnant woman
has been ill for several weeks or, in retrospect, after delivery. At this time, the maternal immune
response to the suspected pathogen may no longer reflect an acute infection—that is, the specific
IgM response is no longer detectable and the IgG response has already reached a plateau.
Neonatal antibody titers are often difficult to interpret because IgG is acquired from the
mother by transplacental passage and determination of neonatal IgM titers to specific pathogens is
technically difficult to perform and not universally available. Paired maternal and fetal-neonatal
IgG titers with higher newborn IgG levels or rising IgG titers during infancy may be used to
diagnose some congenital infections (e.g., congenital syphilis).
If the likelihood of maternal infection with a known teratogenic agent is high, fetal
ultrasound examination is strongly recommended. If the examination demonstrates either a physical
abnormality or delayed growth for gestational age, examination of a fetal blood sample may be
warranted. Cordocentesis can provide a sufficient sample for both total and pathogen-specific IgM
assays or for PCR or culture. The total IgM value is important because the normal fetal IgM level is
less than 5 mg/dL. Any elevation in total IgM may indicate an underlying fetal infection that has
stimulated the fetal immune system. Specific IgM antibody tests are available for CMV, T.
pallidum, parvovirus B19, and toxoplasmosis.
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If maternal serologic studies point to a specific pathogen, it is sometimes possible to detect
the organism in amniotic fluid (culture, PCR). Amniocentesis can be performed and the fluid sent
for analysis. The presence of CMV, Toxoplasma, or parvovirus in amniotic fluid indicates that the
fetus is infected and at high risk, but it does not always mean that the fetus will have severe
sequelae. In contrast, HSV and varicella-zoster virus (VZV) are rarely isolated from amniotic fluid
samples. CMV, Toxoplasma, and parvovirus can also be identified from cordocentesis sampling.
Neonatal infections with CMV, Toxoplasma, rubella, HSV, and syphilis present a diagnostic
dilemma because (1) their clinical features overlap and may initially be indistinguishable, (2)
disease may be inapparent, (3) maternal infection is often asymptomatic, (4) special laboratory
studies may be needed, and (5) appropriate treatment of toxoplasmosis, syphilis, and HSV, which
may reduce significant long-term morbidity, is predicated on an accurate diagnosis. Common
shared features that should suggest the diagnosis of an intrauterine infection include intrauterine
growth restriction, hematologic involvement (anemia, neutropenia, thrombocytopenia, petechiae,
purpura), ocular signs (chorioretinitis, cataracts, keratoconjunctivitis, glaucoma, microphthalmos),
CNS signs (microcephaly, hydrocephaly, intracranial calcifications), other organ system
involvement (pneumonia, myocarditis, nephritis, hepatitis with hepatosplenomegaly, jaundice), and
nonimmune hydrops. Diagnostic studies in newborns with suspected chronic intrauterine infection
should specifically test for each diagnostic consideration. Systemic infections with CMV, HSV, and
enteroviruses frequently involve the liver; if these infections are suspected, liver function tests
should be performed. Neonatal HSV meningitis may be confirmed by isolation of the virus (or by
PCR) from cerebrospinal fluid (CSF) or another site (skin, eye, mouth).
Herpetic infection
Congenital herpetic infection - an uncontrollable infection which is transmitted to the child
at antenatal or at intranatal period. Prevalence of the neonatal herpes is 1 case per 2,5-15 thousand
childbirth. Mortality reaches 50-70%, good prognosis only at 15% of children, others suffer from
severe neurological deficit.
The virus of simple herpes (VSH) 2nd type is the most dangerous. Risk of infection at
primary infection of the pregnant woman is 40-50%, at recurrence - 5-8%. Infection of mother after
32 weeks leads to infection 10% of fetus, before the labour - 40-60% (different permeability of the
placenta). 60-70% of the infected children are infected by contact way. The incubation period is 314 days.
In the absence of specific therapy the lethality at the generalized form can reach 90%, at the
neurologic form -up to 50%. 50% of survived children are disabling.
Clinical symptoms of the generalized infection (GI) are nonspecific and reminds a clinical
picture of neonatal sepsis.
The localized variants develop on the 3rd week of life:
- Hepatic form. Early jaundice with an indirect hyperbilirubinemia, low enzymes (stroma
and reticuloendothelial systems are damaged), alkaline phosphatase raises by 2-3 times. Signs of
cholestasis appear at the initial stage of the disease and progress.
- Cerebral form. Encephalitis. Infants have affection of the brain, neurological disorders of
the older children are characterized with temporal lobes involvement. Further - necroses and cysts,
formation of subependimal cysts are evident.
At intranatal infection children are affected at 18-25 day of life. Pathogenesis: 1) moderate
brain edema (till 3-4 weeks of life), 2) progressing of edema, squeezing, encephalomalation
(infiltrates, necrosis) – 4-5 day of life, 3) progressing expansion of ventricles, development of cysts,
calcificates in white substance of the brain (5 – 6 week of life and later), 4) an atrophy, scarring.
In the clinical picture seizures, drowsiness, hyperexcitability, tremor, poor appetite, signs of
disorder of the pyramidal tract prevail. Survived children have neurologic damages in the form of
delay of psychomotor development, frequently associated with a microcephaly, brain cysts, often
spasticity, and inability to training.
- Mucous and skin form. Vesicular rash on the skin of the trunk, extremities, including
palms, soles, face. Elements at first appear in contact places, and then during 10-11 days extend on
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other parts of the body. New elements of rash can occur for 2-6 weeks. Recurrence is possible for
the first 6 months. Secondary flora can complicate the course of the disease.
- Residual form. Permanent dystrophic affections of the organs owing to the fibrosis,
cirrhosis, scarring. Replacement of the considerable part of the functioning tissue with connecting
tissue occurs. VSH at prenatal acquisition of infection causes severe immunosuppressive action,
suppressing, first of all, a clone of lymphocytes of T4 (helpers), i.e., having the same effect, as HIV
which results in the tendency to septic processes of the different etiology.
Diagnostic valuable for infants is an identification of specific Ig M which doesn’t get
through a placenta.
However, at negative result can't exclude VSH infection.
Causes:
- immaturity of the immune system and immunosuppressive properties of the virus which
leads to the phenomenon of "immunological tolerance" of the fetus and newborn that causes
delayed formation of specific antibodies,
- intranatal infection
Identification of Ig in the first 6 months of life is not informative.
Results of the immunoenzyme analysis, which allow to define a serological profile, only
indirectly can testify to the role of prenatal infections in pathology of infants and can’t serve as the
main criterion of administration of specific etiotropic therapy.
Modern diagnostics consists of molecular DNA/RNA identification of different TORCH
pathogens, by using polymerase chain reaction (PCR).
Results of the PCR can be pseudo-positive owing to the contamination of the studied
material (wrong transportation, storage, etc.), and the pseudo-negative (limited sensitivity of the
used diagnostic test systems and methodical disorders when carrying out the research).
Nevertheless, the DNA/RNA method of diagnostics is regarded as the equivalent of cultural
methods of allocation of the infectious agent.
Cytomegaloviral infection (CMV).
Prevalence in the population - 40 - 100%.
Acquired CMV is characterized by the latent course (except for patients with disordered
immunity in which CMV gets a generalized form).
Congenital CMV – a classical antenatal infection. Unlike other agents of congenital
infections, CMV is capable to cause fetal damage even in the presence of antibodies at the woman.
CMV is the most frequent fetoneopathy among all infectious causes. Virus and antibodies to it are
detected at 1 – 10% of newborns and children of the first three months of life.
CMV belong to the herpes virus of the 5 type. The natural reservoir of the CMV is the
person. The lifelong carriers are lymphocytes. The expressed tropism of CMV is to any epithelial
cells, especially to glandular cells (100% defeat of salivary glands).
Factors of transferring are the saliva ("an illness of kisses"), urine, lacrimal liquid, blood,
vaginal secrets, breast milk, sperm in which the virus remains especially long in high concentration.
Primary infection of the pregnant women occurs seldom; more often latent infection
reactivates caused by immunological disorders, chronic infections, frequent abortions, and frequent
change of sexual partners.
Acquisition of infection by children: >90% - in antenatal period
apprx. 5% - in intranatal period
apprx. 1% - in postnatal period
Virus allocation with urine at prenatal CMV lasts 2-4 years.
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The long time of the relation to CMV was defined by the word "opportunistic infection"
which clinical manifestations are possible only in the conditions of an immunodeficiency. The main
interest to this problem was shown by obstetricians-gynecologists, the neonatology and doctors
under which supervision there were HIV-infected and patients with AIDS. In recent years a
situation changes quite dynamically. CMV quickly leaves for habitually created framework, turning
into a problem which touches professional interests of different experts.
Macroscopic changes aren't specific also the little characteristic. Microscopically all forms
of a cetomegaloviral infection are diagnosed by patognomonical for this infection megalocites. Can
morphologically be lymphoid histocitic infiltrates, granulomas, the centers of
myeloeryhtroblastosis, sclerosis, cystic fibrosis, glandular organs.
Classification
Type
1. Generalized form
- the typical
- typical with incomplete clinical
symptoms
2. The localized form
- Cerebral
- Hepatic
- Pulmonary
- renal
- Mixed
3. Residual
4. Latent form
Course
Acute
Prolonged
Chronic
Latent
If infection occurs before childbirth or intranet period, the child is born with a generalized
form, or generalization develops shortly after the birth. The expressed symptoms of toxicosis,
jaundice, hemorrhagic syndrome, gepatosplenomegaly, CNS, GI, breathing disorders. (Acute caurse
- 3 months, prolonged - 6 months).
If infection took place in the late fetal period and the phase of generalization proceeds at
intranatal period, clinical manifestations answer the localized form and are characterized by
prevailing defeat of any target organ. The localized form is generalized with prevailing defeat of
separate organs. The caurse is acute, prolonged and chronic (it is more than 6 months).
CNS disorder – the most frequent and most adverse syndrome. Encephalitis. As a result of
the transferred neuroinfection at all children the delay of psychomotor and speech development is
formed. At the majority pyramidal disorders, a hypertensive-hydrocefalic syndrome, focal
violations, an atrophy of optic nerves, neurotouch relative deafness remain. Morphologically in a
brain the cysts located more often in peri-and paraventrikular regions, petrificates along the vessels
and in the field of ventricles which distinguish them from petrificates at toxoplasmosis.
At a pulmonary form long processes with development of pulmonary and cardiac
insufficiency, formation of fibrosis and a pneumosclerosis are characteristic.
Result of a hepatic form can be chronic hepatitis which arises as primary and chronic
persistent process more often and proceeds without jaundice with considerable activity of
hepatocellular enzymes and constant hypo - and a disproteinemia. At children with a hepatic form
for the first three years symptoms of dysbacteriosis of intestines, astenoneurotic disorders are noted.
Renal form – interstitsial nephritis, a horseshoe kidney, displastic changes,
micropolycistosis, stenoses of ureters.
Infection in the early fetal period or in the period of organogenesis – the child is born with a
residual form with the created developmental anomalies. Feature of defects is fibrous and cystous
nature of regeneration of organs (cirrhosis, an atresia of biliary tracts, renal cystosis, lungs, cestic
fybrosis). Defects of the embryonic period often incompatible with life. At a residual form process
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is considered finished. It isn't observed virusemia and virus allocations in environment. The virus is
in a latent condition.
At an asymptomatic form in an organism there are morphological and immunological
changes and activator allocations in environment. The clinical symptomatology is absent and there
can be in some weeks and even months of life in the presence of adverse factors, such as infections,
operations, feeding errors (against elimination of maternal antibodies). "The hidden CMVsyndrome": children are born "healthy", however in the remote period they define neurologic
frustration (cerebral spastic infantile paralysis, a delay of intellectual development, violation in
communication, visual impairments, hearing, speech, chronic pathology of a liver). The debut of
congenital CMV can be observed at children after 1 year, in preschool and even school age
Congenital toxoplasmosis
Numerous supervision established fact: the woman can transmit a toxoplasmic infection to
the fetus only 1 time to life, unlike cetomegaloviral and other herpetic infections. (Obviously,
except for immunosupressive women).
Infection of the fetus is possible at primary infection in the first 2 trimesters of pregnancy.
Parazitemi > primary center in a placenta > gematogenic transfer to the fetus. Primary parazitemia
leads to infection in 1/3 cases. Infection before pregnancy is dangerous to the fetus in case of an
immunodeficiency at mother.
Degree of risk of infection increases with gestational age. About 30% of children which are
infected in the intranatal period, have clinically expressed toxoplasmosis at the birth. In other cases
are the asimptomic and latent forms which can give clinical manifestations at any time, including in
months and years. Sometimes consequences of a slow course of toxoplasmic encephalitis become
obvious in initial classes of school (increased fatigue, headaches, are possible spasms). Often
primary demonstration of TI is chorioretinitis.
Clinical manifestations and its degree depends on time of fetal infection.
Classification
Age of patients
Form
Current
From 0 to 3 months of GENERALIZED
life
Meningoencephlic
Acute, subacute
Encephalic
Subacute, chronic
Residual
From 4-5 months to 3 Encephalic
Subacute, chronic
years
Residual
PRESCHOOL
AND Encephalic
Хроническое
SCHOOL AGE
Residual
Generalized form. Appears both from the first days, and at the end of the first, the beginning
of the second month of life. Clinic various. Proceeds hard and can end lethal. Possible transition to
a subsacute and chronic caurse.
Meningoencephalic form. It is observed in the neonatal period or children of the first months
have lives. Proceeds subacutely Subfebrile fever without expressed intoxication, with sufficient
increase in weight. CNS disorder (slackness, drowsiness or concern, eruction, muscular dystonia, a
tremor, paresis, kloniko-tonic spasms, characteristic progressing hydrocephaly) an eye
(iridocyclitis, choreoretinitis, turbidity of a vitreous body, an atrophy of an optic nerve), a
gepatosplenomegalia. The death of the child or invalidization (hydro-, a microcephaly which
progresses, weak-mindedness in combination with paralyzes and epilepsy) can be result.
Encephalic form. It is observed in any age group. Process is characterized by a combination
of already created changes to a lasting chronic or subacute inflammation in CNS. For this form
especially characteristic triad of symptoms - hydrocephaly (is more often internal), intracerebral
calcificates, choreoretiniris (or uveitis). Lag in physical and psychological development,
development hydro-or microcephalia, formation of epileptic seizures is characteristic. At preschool
and school age it is characterized by neurologic syndromes (an underdevelopment of mentality and
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speech, an oligophrenia, violation of statokynetic functions: pyramidal, extrapyramidal, cerebellar,
etc., epileptic seizures), defeat of eyes, neuroendocrine frustration (an illness of Cushing, a
hypothalamic syndrome of the pubertal period, adipozo-genital obesity, a hypophysial nanizm) are
characteristic.
Residual form. Defects of development without signs of lasting pathological process. Babies
and children of early age have anomalies of development often incompatible with life and are at the
bottom of death. Children of advanced age have easier anomalies of development.
Laboratory diagnostics
Toxoplasmosis can be carried to an infection with high level of defeat of the population
(63,7% of adults and 26,8% of children) and low incidence which is caused by opportunistic
character of the activator, causing clinically manifest manifestations, as a rule, in immuno
compromised persons, and also at babies as a result of pre-natal infection.
Congenital chlamidiosis
According to VHO genital chlamidiosis enters into the eight of leading diseases which are
transmitted sexually and takes the second place. Chlamidia - the representative of an intermediate
form of existence.
At the birth 6-7% of children appear the infected chlamidia. At women with chlamidia 4060% of children (VHO) are infected. In the majority of them develop infectious and inflammatory a
disease: conjunctivitis (30-40%), nasopharingitis (15-20%), otites of 10-20%), vulvites (15%),
pneumonia, bronchitis, gastroenteritis, etc. Early diagnostics and early specific therapy is important.
Its absence conducts to development of chronic forms of diseases
Residual form. Defects of development without signs of lasting pathological process. Babies
and children of early age have anomalies of development often incompatible with life and are at the
bottom of death. At children of advanced age - more owing to features of a biological cycle of
chlamidia and morfofunctional immaturity of the baby development of local inflammatory reaction
happens slowly and is shown usually only on 2-4 week of life. At transplacental infection (happens
in case of a massive infection at mother to defeat of pipes, the endometrium, etc.) at the fetus
develops generalized process (meningitis, meningoencephalitis, a carditis, VPS, RDS) the Most
characteristic changes arise in soft brain covers and vascular textures of ventricles ("velvet-like
chorioiditis")
Feature of congenital chlamidiosis is lack of patognomonic signs and not specificity of
clinical symptomatology in the neonatal period.
In the neonatal period: difficulty of adaptation, neurologic violations, respiratory frustration,
edematous, hemorrhagic syndromes, ophthalmopathy, the long and expressed jaundice. The uterine
hypoxia and patrimonial trauma is sometimes perceived as in/.
The greatest value in pathology infected with chlamidiya have ophthalmochlamidiosis and
chlamidial pneumonia.
Conjunctivitis (blennorrhea) arises approximately in 40-50% of children from the infected
women (VHO). This circumstance the caused changes in preprocessing of the baby. Incubatory
period of 5-14 days, acute beginning and long but favorable current. Can become complicated
rhinitis, nazofaringitis, otitis, defeat of other layers of an eye, scarring and a blindness. Chlamidial
pneumonia. Develops at 10% infected. Direct action of chlamidia on pulmonary fabric. The first
symptoms appear in different term: from 5 days about several months. The gradual beginning from
dry unproductive cough which amplifies, gains recurrent character, is accompanied by cyanosis,
vomiting, but without reprises. The general condition suffers slightly. Breath with rattles, but DN
expressed poorly. At an auskultation rattles on all surface, mainly at the end of a breath are listened.
Discrepancy between clinically and radiological (interstitial infiltration, infiltrative shadows) the
expressed pneumonia and minimum expressed symptoms of intoxication. After pneumonia
chlamidiyal myocarditis can develop. Changes in lungs often remain for several weeks and even
months. At prematurely born chlamidial pneumonia proceeds against severe toxicosis and is shown
for 5-7 day of life. The prematurely born can have a cough equivalent – a poperkhivaniye as a result
of concentration of a large amount of slime in the top respiratory ways.
11
Nasopharingitis. It is clinically shown by long cough and rhinitis. Otitis can join. Children with
long cough, with long аденоидами, recidivous antritises have to be surveyed on clamidiosis.
Genital clamidiosis at children is shown a hyperemic mucous membrane without any specific
changes, pain, all-toxic symptoms. The itch and burnings are expressed not always. Characteristic
firmness a hyperemia and mucous or mucopurulent allocations despite careful hygienic actions.
Possible sepsis, meningoencephalitis.
Congenital rubella
Adverse influence on the fetus:
- Teratogenic action
- Spontaneous abortions (10-40%)
- Death (20%)
- Early neonatal mortality (10-25%)
Teratogenic danger of a rubella in the first month of pregnancy makes 35-50%, in the second 25%, in the third - 7-10%. Someone consider that in the first three months of pregnancy danger
comes nearer to 100%. Late teratogenic influence of a virus decreases, but exists.
Classical syndrome of a congenital rubella - Greg's triad (a cataract, heart diseases, deafness).
Except the classical there is an expanded syndrome of VK in which, except three called defects the
set of other anomalies of development enters. In the neonatal period characteristic trombocytopenic
purple which remains from 2 weeks to 3 months. Its frequency is about 15-20%. Thrombocytopenia
happens quite expressed, but is stopped itself and seldom happens a cause of death.
Heart diseases of mainly white type
The cataract can develop after the birth. Sometimes the retina is involved in process but without
irreversible processes.
Most often deafness which quite often connects to a vestibulopathy meets.
Defeats of nervous system aren't always diagnosed at the birth, meanwhile they serious, clinical
demonstration often in the post-neonatal period.
Congenital syphilis
The greatest risk - if mother is ill less than 2 years and also at secondary syphilis mother.
The activator - pale treponema. Transfer way - hematogenic, contact
Classification. Allocate: - fetal syphilis
- early congenital syphilis (demonstration from the birth till 4 years)
- late congenital syphilis (demonstration of 4 years)
- the latent congenital syphilis (can be revealed at any age)
Clinical manifestations: characteristic triad - rhinitis, vesicles, gepatosplenomegaly. Rhinitis - dry,
serous, purulent, with hemorrhagic allocations, puffing. Vesicles on soles, palms in the form of
sluggish bubbles from 3 to 10 mm of copper-colored color on an infiltrative background. There can
be periostites and osteochondrates tubular bones, a pneumonia, haemolytic anemia, cracks in
corners of a mouth, a rectum, fever, choreoretinitis. Can appear on the life 2nd week, but a thicket
on the 2nd month. Quite often begins from concern, causeless shudders, pallor of the skin,
insufficient increase in weight of a body. Developmental anomalies - not characteristic.
Congenital tuberculosis
The activator - Koch micobakteria. Transfer way - hematogenic, at aspiration of the infected
waters. Clinical manifestations: at aspiration infection for the 3rd weeks of life and later intoxication, dysfunction or impassability of intestines, a gepatosplenomegaly, fever, anemia, a
hypotrophy, mechanical jaundice, increase in peripheral and belly lymph nodes, ascites, defeat of
lungs. At hematogen - prematurity, fetal lag in development, anemia, jaundice, a
gepatosplenomegaly, meningitis, pneumonia, kidney insufficiency. Developmental anomalies - not
characteristic.
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5.3 . Diagnostics.
At suspicion on VUI carry out the following complex of inspections:
- The clinical analysis of blood with calculation of quantity of platelets (thrombocytopenia, anemia
and increased to SOY often develop at any perinatal infections);
- The clinical analysis of urine (an infection of urinary ways, pyelonephritis, interstitsial nephritis
very frequent at any perinatal infections);
- Definition in serum of blood of level of the general protein, protein fractions of S-jet protein;
- Tank. blood crops, calla, urine;
- Rentgenography of a thorax at respiratory insufficiency, skulls - at neurologic symptomatology;
- Determination of activity in blood of gepatospecific enzymes - at a gepatomegaly.
- Obligatory survey by the oculist.
- Considering the high frequency of defeat of a brain and its covers at VUI, usually shown lumbar
puncture if the patient has any not clear neurologic symptomatology. It is expedient to make and a
neurosonography as, for example, at a cymegaly find quite specific changes - one or several cysts,
calcificates round brain ventricles.
- Determination of functional properties of neutrophils and level of immunoglobulins in blood
serums:
(in umbilical blood the raised level of immunoglobulins M (it is more 0,03ú/l);
(there are immunoglobulins A (at healthy newborns they are absent);
- Serological researches in dynamics in 10-14 days (pair serums) at mother and the child,
carried out for the purpose of identification of existence of antibodies of Ig to viruses,
mycoplasmas, listeria, toxoplasma, spitichets. and etc. Only at increase in a caption of antibodies at
the child in 10-14 days by 4 times also it is more possible to speak about the active infectious
process caused by the activator, to which revealed increase of a caption of antibodies.
Identification of specific Igм to this or that activator at the child of the first week of life - the
indisputable proof of a pre-natal infection.
Diagnostics at toxoplasmosis:
Ig to Tox revealed by any methods testify to the fact of the previous infection. Maternal Ig to
Tox at children in some cases can remain till 9-12 masses. Can be used only as screening method.
Igм to Tox also have no independent diagnostic value as aren't always accompanied by
replikativny activity, at part of patients can remain for the long period (of 8 months)
IgA identification to Toxo can have diagnostic value in the presence of clinical symptoms.
Perspective stage of development of serological diagnostics is application a western-blota that
gives the chance to distinguish maternal Ig to Toxo from own Ig to Toxo of the child (directed
against different proteins токсоплазмы).
The main laboratory criterion is identifications of DNA of Toxo at blood and urine by PCR.
And some authors note that identification of DNA of Toxo in urine is 25% more effective, than in
blood
However for definition of medical tactics and the disease forecast laboratory data have to be
considered at the same time and in a complex from clinical and (behind indicators) tool data.
Characteristic tool signs:
Kalcificates appear in different departments of CNS, mainly in hemispher. Usually appear in
some weeks or months after the birth.
The anizoorbital syndrome is characterized by a divergence in size of orbits at the patient
most often at the identical size of eyeballs
Hydrocephaly. Internal or external.
SHV, CMV, rubella can cause chorioretinitis, bring to hydro-, to a microcephaly, formation brain
calcificates. In establishment of etiological accessory will play a role laboratory data. Rather
reliable distinctive symptom of congenital toxoplasmosis - sharp increase in protein in spinal liquid
At suspicion on CMV:
a) absolutely available, high-specific and quite sensitive method - a cytoskopy of urine, a saliva
with identification of the cages transformed on huge type ("an owl's eye").
13
b) The most correct equivalent is PCR with different substrata. Today criterion of an initiation of
treatment, its efficiency, weight of a condition has to become definitions of virus loading as it
becomes at the PITCHFORK-infected patients.
c) Definition of antibodies to CMV by IFA.
Diagnostics of congenital chlamidiosis based on anamnestic data, clinical manifestations,
laboratory researches.
- Cytoskopic method (identification of cytoplasmatic inclusions in cytoplasm of the struck
cages of an epithelium (conjunctiva... )
- Cultural method ("the gold standard")
- Immunochemical methods (identification of anti-gene substances in a material) IFA,
mutual fund, NIF
- Molecular and biological (PLR)
- Serological (identification antichlamidial and/t). More informative definition of Iga.
Maternal Ig at a congenital rubella disappear till 1 year. Diagnostic valuable increase of a
caption of Ig, Igм identification, positive PLR.
The diagnosis of VUI confirms activator allocation with
- blood (bacteria, respiratory viruses),
- urine (cytomegalovirus, mycoplasmas, bacteria),
- nasopharynx washouts (viruses of a rubella, herpes, enteroviruses, respiratory viruses),
- gastric juice, calla (enteroviruses, bacteria),
- contents of vesicles (herpes viruses),
- cerebrospinalny liquid (toxoplasma, viruses of a rubella, herpes, enteroviruses, mycoplasmas,
bacteria);
- its identification in dabs prints of allocations from an eye (chlamidia).
As unconditional confirmation of VUI methods of molecular diagnostics of DNA/RNA
different TORCH infections, in particular a method of polimerase chain reaction today can serve.
Result receive much quicker, but it is desirable to treat it together with data of specific
immunological inspection.
5.4 . Treatment.
Specific therapy at VUI possible only after statement of the nosological diagnosis, as a rule,
confirmed with immunological and/or microbiological researches.
Toxoplasmosis.
Specific therapy has to be carried out in each case of congenital toxoplasmosis or pre-natal
infection токсоплазмами, even when there is a subclinical or latent current. Preparations and doses:
Pirimetamin (darapry, chloridin) +sulfadimesin - 4 - a 6-week course.
Chloridin in the first 2-3 days is given in the unloading dose 2 mg/kg/days divided into two intakes,
the preparation in a dose of 1 mg/kg/days (in two doses for intake) once in 2-3 days, as the period of
semi-removal of a preparation from an organism about 100 hours is farther.
By Sulfadimezin appoint in a dose 50 - 100 mg/kg/days in 2 or 4 intakes. For prevention of
hematologic toxicity of chloridin and сsulfadimesin twice for a week give inside folic acid inside or
parenteralno in a dose of 5 mg (calcium leicovorin).
Spiramitsin (an antibiotic from group of macroleads) - 1-11/g. Monthly course in a dose of 100 mg /
кг\сутки, divided into 2 intakes.
Corticosteroids (Prednisolonum) in the dose of 1,5-2,0 mg/kg/days divided into two intakes (in the
morning and in the afternoon), appoint at the proved active inflammatory process to its resolution
(in particular, to decrease in level of protein in a liquor to 1 g/l or to a visual resolution of
chorioretinitis). Dose reduce gradually and cancel.
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Herper virus infection.
At infectious processes at the babies caused by viruses of simple herpes I and II type, and also at
congenital chicken pox the shown specific therapy as system (an acyclovir or vidarabin), and local
at defeat of eyes.
Acyclovir (acycloguanosin, zovirax, viralex) to babies optimum to enter intravenously (on an extent
of hour) in the daily dose of 30 mg/kg divided into 3 injections, but prematurely born with a mass
of a body less than 1500 - 20 mg/kg on the 2nd introduction, 2-3 weeks depending on effect.
Vidarabin (adeninarabinozid) - cytostatics, oppresses reproduction of viruses of herpes at the
expense of DNA polymerase blockade.
At herpetic defeat of eyes local use eye drops: 1% solution iodine dioxyuridine, 3% vidarabine, 12% trifluridine.
Duration of specific antirecurrent treatment by anti-herpetic preparations not established also
recommend to be guided by results of virologic researches at the patient.
Cytomegaloviral infection
At the CMV application of specific anticytomegaloviral immunoglobulin of Biotest Farma firm
(Germany) - Cytotect can be considered as rather effective and safe method of treatment only. Enter
Cytotect intravenously in a dose of 2 ml/kg each 2 days or to 4 ml/kg there are each 4 days to
obvious return development of clinical symptoms of CMV.
Ganciklovir (Cymevin) - cyclic analog of guanosine, inhibiting a cytomegalovirus DNA
polymerase and by that its replication. Enter intravenously (for an hour) in a dose of 5 mg/kg 2
times per day: 14-21 days and further preparation give a course inside in a dose of 5 mg/kg per day.
At babies ganciclovir through toxicity apply only at such course of disease which threatens life.
Chlamidiosis.
At conjunctivitis of the baby - 0,5% erintromitse eye ointment (or 0,5% solution of levomycetin)
isn't more rare than 5-6 times a day, erythromycin inside (erygran) or in candles in the dose of 50
mg/kg/days divided into 4 receptions, for 14 days. At system introduction of erythromycin (at
pneumonia) locally it is possible not to appoint it.
Mycoplasmosis. Are shown purpose of erythromycin (50 mg/kg / a time) or azythromicin (5
mg/kg once per day inside, but in the first day 2 times per day; duration of a course is 5-10 days).
Levomicetin and тетрациклины recommend to appoint only at micoplasmic meningoencephalitis
and severe pneumonia.
At congenital syphilis or the birth of the child from mother with active syphilis during
pregnancy conduct 6 two-week courses (with the same intervals between them) penicillin in a daily
dose 50000 FROM/kg, divided into 4 injections.
5.5 . Forecast. Prevention.
At early diagnostics and active treatment of CI the forecast for life, as a rule, favorable, and for an
absolute recovery - not clear. After transferred virus CI the activator persists for months and years,
contributing to the most different diseases (to an illness of connecting fabric, kidneys, etc.).
Prevention:
- treatment of an urinogenital infection at women of genital age to pregnancy approach.
- observance during pregnancy of elementary sanitary and hygienic rules, including in the
sexual relations.
- double carrying out sedimentary tests on syphilis and existence of complement binding
antibodies with toxoplasmic anti-gene.
- Treatment of extragenital diseases of mother.
- Sanitation of the centers of an infection.
- Accurate conducting childbirth.
- Restriction of contact with animals.
15
Additional materials for the self-control
А. Clinical cases
Case 1
A boy born post-term weighing 3.6 kg with normal Apgar scores was noticed to have
generalised skin petechiae at birth but no other obvious clinical abnormalities. On investigation, he
had thrombocytopenia (platelet count 29×109/l), but other haematological markers were normal. He
was discharged after bacterial sepsis and alloimmune thrombocytopenia had been excluded.
Unfortunately there was not sufficient blood available to investigate for congenital viral infections.
Thrombocytopenia resolved spontaneously at age 16 days (platelet count 176×109/l).
The infant was readmitted at 10 weeks of age for poor feeding, diarrhoea, and occasional vomiting.
On examination he was found to be pale and thin; weight was at the 4th percentile. He had mild
hepatosplenomegaly, a soft systolic murmur, mild anaemia (haemoglobin 98 g/l), and slightly
abnormal results on liver function tests (aspartarte aminotransferase 75 U/l, alanine
aminotransferase 97 U/l, and alkaline phosphatase of 602 U/l). There was no evidence of hepatitis B
surface antigen, hepatitis A IgM, hepatitis C IgG, toxoplasma IgA, or IgG antibodies in serum.
Cytomegalovirus and parvovirus B19 IgG were detected in serum, suggesting either passive transfer
of maternal antibodies or past infection. Interestingly, rubella IgM antibody was strongly positive in
serum and rubella IgG was also positive.
The infant’s mother recalled attending hospital at 11 weeks’ gestation with fever, swollen
left knee, and a macular rash starting on the face and spreading to the trunk and abdomen, which
was considered to be a drug reaction.
Questions
1 What is your first suspected diagnosis?
2 How do you confirm that this infection is congenital and was not acquired postnatally?
3 How this disease could be prevented?
Case 2
A boy, gestational aged 34 weeks and 4 days, was born at an outlying hospital and
transferred to the neonatal intensive care unit for evaluation of extensive skin lesions noted at
delivery. The lesions were described as numerous blisters, large bullae and extensive areas of
scarred skin on the trunk, anterior chest, back and extremities. Several lesions were hemorrhagic
and weeping in appearance.
The infant was born to a group B streptococcal status unknown, rapid plasma reagin
nonreactive, rubella immune, HIV-negative, 26-year-old woman with a history of chickenpox as a
child. This was the woman’s first pregnancy and the child was delivered via primary cesarean
section after premature rupture of membranes.
The pregnancy was complicated by a first genital herpes simplex virus (HSV) type 2
infection at 11 weeks gestation that was treated with a five-day course of intravenous acyclovir. She
had multiple recurrences requiring intermittent treatment with oral acyclovir then valacyclovir and
was placed on a daily suppressive regimen of valacyclovir for the final month of pregnancy.
Though she had no lesions consistent with HSV at the time of labor, the patient opted for cesarean
section to reduce the risk of vertical transmission. Other medications taken during pregnancy
included 25 mg promethazine for ongoing nausea, bupropion 150 mg for depression and 6 mg/day
hydromorphone for chronic pain secondary to idiopathic pancreatitis and colitis of unclear etiology.
She also reported moderate tobacco and alcohol use during pregnancy. The delivery itself was
essentially unremarkable, Apgar scores were 8 and 9 and the infant transitioned well.
On arrival in the NICU at 9 hours of life, the infant was febrile to 100.4°F and was breathing
comfortably on room air with no signs of distress. The infant appeared appropriate for gestational
age with a weight 2499 g, and was appropriately alert and active. There were no dysmorphic
features, and the head circumference of 31 cm was normal for the gestational age. Examination of
the skin revealed bullae, grouped vesicles on erythematous bases and patches of crusted lesions on
the scalp, cheeks, trunk, chest, back and extremities. There were no lesions of the mouth, eyes,
16
nares, ear canal or genital area. The liver and spleen were both firm and palpable 3 cm to 4 cm
below the costal margin. He was irritable only when the skin was disturbed. The remainder of
physical exam was unremarkable.
Questions
1. What is your presumable diagnosis?
2. How to confirm it?
3. How this disease could be prevented?
4. How to treat the child?
B. Tests
Question 1. Causes of megalocephaly include all of the following except:
A. Thalassemia
B. Chronic subdural effusions
C. Hydrocephalus
D. Canavan disease
E. Congenital CMV infection
Answer E. Explanation: Congenital cytomegalovirus (CMV) infection usually causes
microcephalus, not macrocephalus. Expansion of the bone marrow (hemolytic anemias), storage
diseases (lysosomal, leukodystrophies), excessive cerebrospinal fluid (CSF) (hydrocephalus),
intracranial bleeding (subdural), and familial factors contribute to megalocephaly.
Question 2. Which of the following is the recommended treatment for neonatal listeriosis?
1. Ceftriaxone
2. Ampicillin with or without an aminoglycoside
3. Cefotaxime with or without an aminoglycoside
4. Erythromycin
5. Vancomycin
Answer B. Explanation: Listeria isolates are usually sensitive to penicillin, ampicillin,
erythromycin, and tetracycline but are not susceptible to the cephalosporins, including the thirdgeneration cephalosporins. The addition of an aminoglycoside (e.g., gentamicin) lowers the
minimum bactericidal concentration.
Question 3. A 2-wk-old neonate experiences high fever, severe respiratory distress, and
hepatomegaly. The chest film shows a fine, nodular infiltrate throughout both lungs, and congenital
tuberculosis is suspected. All of the following are expected additional findings in this newborn
except:
A. Positive PPD skin test result
B. Positive PPD skin test results in family members
C. Acid-fast organisms on gastric aspirate
D. Meningitis
E. Hepatitis
Answer A. Explanation: The PPD test usually does not yield positive results initially in children
with congenital tuberculosis, but results become positive in 1-3 mo. The most important clue to
diagnosis is a family history of tuberculosis.
Question 4. The mother of a newborn is found to have an abnormal-appearing admission chest
film and acid-fast bacilli on sputum smear. The mother has no other symptoms and is ready to be
discharged from the hospital and is willing to comply with her recommended treatment. The
recommended management strategy for the newborn is to:
1. Treat the mother and isolate her from the newborn until she has been treated for 2 wk.
2. Treat the mother and isolate her from the newborn until she has three consecutive negative
sputum smears and cultures.
17
3. Treat the mother; no isolation is necessary.
4. Treat the mother and treat the infant with isoniazid and rifampin for 6 mo, with pyrazinamide
during the first 2 mo; no isolation is necessary.
5. Treat the mother and treat the infant with isoniazid until the mother is sputum culture-negative
for 3 mo; no isolation is necessary.
Answer E.Explanation: Isoniazid therapy for newborns has been so effective that separation of the
mother and infant is no longer mandatory unless the mother is ill enough to require hospitalization
or is expected not to adhere to her treatment regimen.
Question 5. In a newborn whose mother was treated for syphilis during pregnancy, all of the
following are risk factors for congenital syphilis except:
A. Treatment of the mother with erythromycin
B. Treatment of the mother with doxycycline
C. Change in maternal VDRL titer from 1:32 at treatment to 1:16 at delivery
D. Treatment of the mother more than 30 days before delivery
E. VDRL titer 1:32; RPR negative.
Answer D. Explanation: Risk factors for congenital syphilis are maternal treatment that was
inadequate, unknown, or undocumented; treatment given at less than 30 days before delivery;
treatment with a nonpenicillin regimen; and serial maternal VDRL titers that do not decrease
sufficiently (at least fourfold) to demonstrate a cure.
Question 6. A full-term male newborn whose mother had reactive Venereal Disease Research
Laboratory (VDRL) and microhemagglutination assay-Treponema pallidum (MHA-TP) results at
the time of delivery was evaluated. He was anemic and had thrombocytopenia and mild
hepatomegaly. He also had a desquamative skin rash consistent with congenital syphilis. His CSF
was clear, with 5 white blood cells (WBCs), 0 RBCs, protein of 80 mg/dL, and glucose of 49
mg/dL; the CSF VDRL result was nonreactive. Based on this examination, which of the following
is true?
A. The newborn has symptomatic congenital syphilis but not neurosyphilis and can therefore be
treated with benzathine penicillin.
B. The newborn may be treated with a combination of ampicillin and gentamicin for 7 to 10 days.
C. Neurosyphilis cannot be excluded in this newborn; therefore, he should be treated for
neurosyphilis.
D. All cases of neurosyphilis would have CSF pleocytosis and a reactive CSF VDRL result.
E. An MHA-TP test of the CSF is necessary to diagnose neurosyphilis.
Answer C. Explanation: This infant requires a complete course of therapy for neurosyphilis.
Question 7. All of the following are characteristic manifestations of congenital rubella syndrome
except:
1. Snuffles
2. Intrauterine growth retardation
3. Cataracts
4. Structural cardiac defects
5. Sensorineural hearing loss
Answer A. Explanation: Congenital rubella affects virtually all organ systems. Snuffles is a sign of
congenital syphilis.
Question 8. Which of the following statements regarding neonatal enterovirus infections is true?
A. They are much less common than infections due to herpes simplex virus and cytomegalovirus
B. They are invariably mild, benign illnesses
C. They are best treated with ribavirin
D. They may cause life-threatening hepatitis and coagulopathy
E. They generally occur only in extremely low birthweight infants
18
Answer D. Explanation: Most symptomatic neonates with neonatal enterovirus infection have
benign courses, but a minority has severe disease that may be dominated by any combination of
sepsis, meningoencephalitis, myocarditis, hepatitis, coagulopathy, and pneumonitis.
Question 9. All of the following statements regarding herpes simplex virus (HSV) infections in
neonates are true except:
A. Most cases are caused by HSV type 2
B. Women with primary HSV genital tract infection are more likely to transmit infection to their
offspring than women with recurrent HSV infection
C. Most mothers of newborns with perinatal HSV infection have a history of genital HSV infection
D. Most mothers of newborns with perinatal HSV infection are asymptomatic at delivery
E. Most cases are transmitted at delivery and are not true congenital infections
Answer C. Explanation: Only 15-20% of mothers of newborns with perinatal HSV have a history of
obvious HSV infection, and only about 25% have any relevant symptoms at birth.
Question 10. Recommended management for a mother with active genital HSV infection during
labor is:
A. Culture of blood from the newborn, with treatment based on culture results
B. Culture of blood from the newborn, with empirical acyclovir therapy
C. Intravenous acyclovir treatment for the mother
D. Cesarean section within 4 hr of rupture of membranes
E. Intravenous acyclovir treatment for the mother and cesarean section within 4 hr of rupture of
membranes
Answer D. Explanation: Both the American Academy of Pediatrics and the American College of
Obstetrics and Gynecology recommend cesarean section if primary, first-episode, or recurrent HSV
lesions are present on the mother at the onset of labor. Only 15-20% of mothers of newborns with
perinatal HSV have a history of HSV infection.
Question 11. A neonate is 5 days old. What vaccination dose of BCG vaccine (in мg) is necessary
for vaccination of this child?
A 0,05 мg
B 0,025 мg
C 0,075 мg
D 0,1 мg
E 0,2 мg
Question 12. A 6 week old child is admitted because of tachypnea. Birth had been uneventful,
although conjunctivitis developed on the third day of life and lasted for about 2 weeks. Physical
examination reveals tachypnea, bilateral inspiratory crackles and single expiratory wheezing.
Bilateral pneumonia is evident on chest X-ray. The child is afebrile and has no history of fever.
White blood cell count is 15х109/l, with 28\% of eosinophils. The most likely cause of this child's
symptoms is:
A Clamydia trachomanis
B Pneumocystis carinii
C Mycoplasma pneumoniae
D Visceral larva migrans
E Varicella
Question 13. The boy was born at asphyxia at 40 weeks` gestation from 6th complicated
pregnancy (risk of abortion, gestosis of Іth and IIth halves of pregnancy), from 3rd delivery.
Mother is 40 year old. A condition of the child is severe, weight is 2 kg, signs of immaturity,
hydrocephaly. Skin is pale and yellow, acrocyanosis. Heart sounds are faint, coarse systolic murmur
19
in all points of auscultation. The abdomen is increased, the liver is +3 cm. Urine is of intense color,
feces is light. Horioretinitis is detectes by the. What is your preliminary diagnosis?
A Congenital toxoplasmosis
B Haemolytic disease of the newborn
C Sepsis
D Congenital heart disease
E Congenital hepatitis
4. LITERATURE FOR STUDENTS
1. Nelson Textbook of Pediatrics. - 18th ed. / Ed. by R. Kliegman et al.-Philadelphia: Saunders Co,
2007.- 3146 p.
2. Pediatry. Guidance Aid / За ред. О.В. Тяжка; О.П. Вінницька, Т.І. Лутай – К. : Медицина, 2007 . – 158
с.
3. Current Pediatric Diagnosis & Treatment (CPDT). - 18th ed./ Ed. By W.W.Hay et al. - The
McGraw-Hill Companies. – 2006.
4. Current pediatric therapy -18th ed. / Ed. by F.D.Burg et al. - Elsevier Inc. – 2007.
5. Nelson Essentials of Pediatrics -5th ed. / Ed. by B.S.Siegel, J.J.Siegel. - Elsevier Inc. – 2007.
6. Examination of the Newborn. A Practical Guide / Ed. by Helen Baston and Heather Durward. the Taylor & Francis e-Library. - 2005.
7. Fetal and neonatal secrets. - second edition . / Ed. by R.A.Polin, A.R.Spitzer. - Elsevier.- 2006.
8. Key Topics in Neonatology / Ed. by R.H. Mupanemunda, M. Watkinson. - Oxford Washington
DC. -1999.
Performed by ass. Shiricina M.V., ass. Tkachenko N.P.
Approved “_____”____________20____y.
Сhief of the department, professor
Protocol №_____
V. A. Kondratyev
Reconsidered
Approved “_____”____________20____р.
Сhief of the department, professor
Protocol №_____
V. A. Kondratyev
Reconsidered
Approved ““_____”____________20____р.
Сhief of the department, professor
Protocol №_____
V. A. Kondratyev
Reconsidered
Approved “_____”____________20____р.
Сhief of the department, professor
Protocol №_____
V. A. Kondratyev
20