ClinicoPathological ConferencClinicoPathological Conferencee

93-03-2493-03-24

林世朋 林世朋 / / 蔡明志大夫蔡明志大夫三 軍 總 醫 院 小 兒 部三 軍 總 醫 院 小 兒 部

Chief complaintsChief complaints

A A 4-day-old4-day-old girl had suffered from fever girl had suffered from fever since two days agosince two days ago

Present illness (1)Present illness (1) The 4-day-old female newborn was a fullterm and was deliverThe 4-day-old female newborn was a fullterm and was deliver

ed vaginally through ed vaginally through thick meconiumthick meconium, with Apgar score of 9 at , with Apgar score of 9 at 1 minute and 9 at 5 minute.1 minute and 9 at 5 minute.

She developed a She developed a fever of 38.6 ‘Cfever of 38.6 ‘C at 2 days of age, but was rela at 2 days of age, but was relatively well tively well without cardiopulmonary compromise.without cardiopulmonary compromise.

She was sent to hospital for help where septic workup was donShe was sent to hospital for help where septic workup was done including lumbar puncture. Viral cultures were submitted bee including lumbar puncture. Viral cultures were submitted because of cause of several papulovesicular lesions noted on her back.several papulovesicular lesions noted on her back.

Ampicillin & gentamicine therapy was started at 2 days of age Ampicillin & gentamicine therapy was started at 2 days of age and acyclovir was added at 4 days of age.and acyclovir was added at 4 days of age.

All cultures including viral culture were negative.All cultures including viral culture were negative.

Present illness (2)Present illness (2)

Then she was transferred to another hospital for further Then she was transferred to another hospital for further evaluation.evaluation.

In addition, the mother had In addition, the mother had mild fever at the time of deliverymild fever at the time of delivery, , and was and was treated with antibioticstreated with antibiotics briefly before discharge. briefly before discharge.

By telephone interview, the mother said that she was By telephone interview, the mother said that she was still still febrile 1 week after deliveryfebrile 1 week after delivery with the main symptoms of with the main symptoms of malaise, abdominal pain and headachemalaise, abdominal pain and headache..

She denied respiratory symptoms, vomiting, diarrhea and skin She denied respiratory symptoms, vomiting, diarrhea and skin rash. rash. The father believed that she was jaundicedThe father believed that she was jaundiced..

Present illness (3)Present illness (3)

The baby continued to appear pale, ill and febrile. On The baby continued to appear pale, ill and febrile. On the baby’s 10th day of life, the mother visited the the baby’s 10th day of life, the mother visited the nursery.nursery.

With ill appearance, she told us that she had With ill appearance, she told us that she had headache headache and neck pain.and neck pain.

The father stated that she was having The father stated that she was having personality personality changeschanges that began the week before delivery. that began the week before delivery.

The mother was then admitted to our hospital and The mother was then admitted to our hospital and evaluations revealed the diagnosis. evaluations revealed the diagnosis.

Past, personal and family historiesPast, personal and family histories

Fullterm with gestational age of 38 weeks Fullterm with gestational age of 38 weeks via vaginal delivery.via vaginal delivery.

Apgar scores : 9 & 9 at 1st & 5th minutes, Apgar scores : 9 & 9 at 1st & 5th minutes, respectively ; BBW : 3100 g respectively ; BBW : 3100 g

Mother history : a 24-year-old gravida 3, pMother history : a 24-year-old gravida 3, para 1 to 2 mother.ara 1 to 2 mother.

Contact history : unknownContact history : unknown Traveling history : unknownTraveling history : unknown Family history : unknownFamily history : unknown

Physical examinationsPhysical examinations(4 days of life)(4 days of life)

Vital signs :Vital signs :HR : 130 /min ; RR: 40 /min ; BT: 38.6 ‘CHR : 130 /min ; RR: 40 /min ; BT: 38.6 ‘C

General appearance : General appearance : pale and ill-looking, fussy pale and ill-looking, fussy but consolablebut consolable

Skin : several Skin : several scabbing lesions on her scalpscabbing lesions on her scalp.. Chest : clear and symmetric breathing sound; taChest : clear and symmetric breathing sound; ta

chypnea: (-) ; retraction :(-)chypnea: (-) ; retraction :(-) Abdomen : Abdomen : palpable liver edgepalpable liver edge, 4 cm below the ri, 4 cm below the ri

ght costal margin in the midclavicular line; ght costal margin in the midclavicular line; palpapalpable spleen tipble spleen tip, 3 cm below the left costal margin., 3 cm below the left costal margin.

Genitalia : Genitalia : bilateral inguinal lymph nodesbilateral inguinal lymph nodes 0.5 cm 0.5 cm in diameter in diameter

Laboratory findings (1)Laboratory findings (1) At 3 days of age :At 3 days of age :

WBC : 13400 /mm3WBC : 13400 /mm3Platelet : 96000 /mm3Platelet : 96000 /mm3Neutrophil : 48%Neutrophil : 48%Lymphocytes : 17 %Lymphocytes : 17 %Band form : 29% Band form : 29% (<15 %)(<15 %)

ALT : 20 U/L ALT : 20 U/L (6-50 U/L)(6-50 U/L) CSF studyCSF study : :

WBC: 4 /mm3 (all mononuclear cells)WBC: 4 /mm3 (all mononuclear cells)Protein : 91 mg/dl (84 Protein : 91 mg/dl (84 ±± 45 mg/dL) 45 mg/dL)Glucose : 49 mg/dl (46 Glucose : 49 mg/dl (46 ±±10 mg/dL)10 mg/dL)

Laboratory findings (2)Laboratory findings (2)

At 6 days of lifeAt 6 days of life

CBC : essentially unchangedCBC : essentially unchangedAST : 66 U/L (35-140 U/L)AST : 66 U/L (35-140 U/L)ALT : 54 U/L (6-50 U/L)ALT : 54 U/L (6-50 U/L)r- GT : 555 U/Lr- GT : 555 U/L (13-147 U/L) (13-147 U/L)

Problems of neonateProblems of neonate

Major problems :Major problems : Fever Fever Skin lesions Skin lesions (papulovesicula(papulovesicula

r)r) over the back; scabbi over the back; scabbing lesions on the scalpng lesions on the scalp

HepatosplenomegalyHepatosplenomegaly Lymphadenopathy over Lymphadenopathy over

inguinal regionsinguinal regions

Minor problems :Minor problems : Predominant band form Predominant band form

of WBCof WBC ThrombocytopeniaThrombocytopenia Heavy meconium stainHeavy meconium stain

Problems of motherProblems of mother

Major problems :Major problems : Personality changesPersonality changes Fever when delivery s/p Fever when delivery s/p

antibiotic therapyantibiotic therapy Still fever, malaise, Still fever, malaise,

abdominal pain and abdominal pain and headacheheadache

Headache and neck pain.Headache and neck pain.

Minor problems :Minor problems : JaundiceJaundice

Questions ??Questions ??

Neonate :Neonate :1. any other abnormal physical findings ?1. any other abnormal physical findings ?2. head circumference ?2. head circumference ?3. ophthalmoscopic examination ?3. ophthalmoscopic examination ?4. other laboratory findings 4. other laboratory findings (Hg, bilirubin etc..)(Hg, bilirubin etc..)

5. CxR ?5. CxR ?6. CNS image studies ?6. CNS image studies ?

Question ??Question ?? Mother :Mother :

1. PROM ? Amnionitis ?1. PROM ? Amnionitis ?2. Liver function ? Bilirubin levels ?2. Liver function ? Bilirubin levels ?3. fever source ? Genital cultures ?3. fever source ? Genital cultures ?4. culture results ?4. culture results ?5. physical findings ? Neurologic findings ? 5. physical findings ? Neurologic findings ? 6. Lumbar puncture ? CSF studies results? 6. Lumbar puncture ? CSF studies results? 7. past & personal histories ? VDRL ?7. past & personal histories ? VDRL ?8. travel & contact histories ?8. travel & contact histories ?9. Image study (CxR, brain CT)? 9. Image study (CxR, brain CT)? 10. What kind of antibiotics were used when10. What kind of antibiotics were used when delivery ? Drug history ? delivery ? Drug history ?

Hepatosplenomegaly Lymphadenopathy Skin lesions ThrombocytopeniaRubella Rubella Rubella Rubella

T. pallidum T. pallidum T. pallidum T. pallidumEnterovirus Enterovirus Enterovirus

HIV HIV Measles HIVCMV CMV VZV CMVHSV HSV HSV

Plasmodium Toxoplasmosis ToxoplasmosisT. cruzi

Rubella T. pallidum Enterovirus HIVCMV HSV

Possible organisms:

Possible Consequences of Possible Consequences of Infection of a MotherInfection of a Mother

Infection of pregnant mother

Fetus not infected Fetus infected Placenta infected

Fetus not infectedDeath as embryo/fetus Congenitally infected live birth

Congenital disease/syndrome

Resolution of symptoms/sequelaeof congenital disease

Persistent infection withProgressive/late-onset sequelae

Normal-appearing infant

Possible organismsPossible organisms

Bacteria :Bacteria :Trepnema pallidum, MycobacteriumTrepnema pallidum, Mycobacterium tuberc tuberculosisulosis

Virus :Virus :Rubella, CMV, HSV, HIV, EnterovirusRubella, CMV, HSV, HIV, Enterovirus

Protozoa :Protozoa :Toxoplasma gondii, PlasmodiumToxoplasma gondii, Plasmodium

Clinical Features of Prenatal Clinical Features of Prenatal TORCH InfectionTORCH Infection

Relative Clinical Features of Relative Clinical Features of TORCH InfectionTORCH Infection

Congenital Rubella SyndromeCongenital Rubella Syndrome Affect virtually all organ systemsAffect virtually all organ systems Manifestations :Manifestations :

11.IUGR (most common).IUGR (most common)2.cataracts, frequently associated with microphthalmia 2.cataracts, frequently associated with microphthalmia 3.myocarditis and structural cardiac defects 3.myocarditis and structural cardiac defects (PDA or pulmonary artery stenosis)(PDA or pulmonary artery stenosis)4.”blueberry muffin” skin lesions4.”blueberry muffin” skin lesions5.hearing loss from sensorineural deafness5.hearing loss from sensorineural deafness6.meningoencephalitis6.meningoencephalitis7.pneumonia, hepatitis, bone lucencies, thrombocytopenia7.pneumonia, hepatitis, bone lucencies, thrombocytopenia purpura, and anemia. purpura, and anemia.8.motor and mental retardation8.motor and mental retardation

Diagnosis :Diagnosis :1.anti-rubella IgM Ab in neonatal serum1.anti-rubella IgM Ab in neonatal serum2.culturing rubella virus from the infant (nasopharynx, urine, 2.culturing rubella virus from the infant (nasopharynx, urine, or tissue)or tissue)

Cytomegalic Inclusion DiseaseCytomegalic Inclusion Disease Congenital CMV infectionCongenital CMV infection Only 5% of all congenitally infected infants have severe cytomegalic Only 5% of all congenitally infected infants have severe cytomegalic

inclusion disease, another 5% have mild involvement, and 90% are inclusion disease, another 5% have mild involvement, and 90% are born with subclinical, but still chronic, CMV infection.born with subclinical, but still chronic, CMV infection.

Characteristic manifestations : Characteristic manifestations : IUGR, prematurity, IUGR, prematurity, hepatosplenomegalyhepatosplenomegaly and jaundice, and jaundice, thrombocytothrombocytopeniapenia and purpura, and microcephaly and and purpura, and microcephaly and intracranial calcifications.intracranial calcifications.

Other neurologic problems :Other neurologic problems :chorioretinitis, sensorineural hearing loss, and mild increases in CSF chorioretinitis, sensorineural hearing loss, and mild increases in CSF proteinprotein

Most symptomatic congenital infections and those resulting in sequMost symptomatic congenital infections and those resulting in sequelae are caused elae are caused by primaryby primary rather than reactivated infections in pre rather than reactivated infections in pregnant womengnant women

Re-infection with a different strain of CMV can lead to symptomatic cRe-infection with a different strain of CMV can lead to symptomatic congenital infection. ongenital infection.

Asymptomatic congenital CMV infection is likely a leading cause of sAsymptomatic congenital CMV infection is likely a leading cause of sensorineural hearing loss, which occurs in approximately 7% of infeensorineural hearing loss, which occurs in approximately 7% of infected infants.cted infants.

Human Immunodeficiency Virus (1)Human Immunodeficiency Virus (1)

Currently, >95% of children with HIV infection acquire Currently, >95% of children with HIV infection acquire the infection from their mother the infection from their mother (vertical transmission)(vertical transmission); ; transfusion of contaminated blood or clotting factor transfusion of contaminated blood or clotting factor concentrates is now rarely observed in the USAconcentrates is now rarely observed in the USA

Breastfeeding remains a possible risk for transmission.Breastfeeding remains a possible risk for transmission. Infants born to HIV-infected mothers :Infants born to HIV-infected mothers :

1. Risk of infection is 13-39% if no antiretroviral therapy1. Risk of infection is 13-39% if no antiretroviral therapy delivered to mother and infant delivered to mother and infant2. With appropriate therapy, risk is < 5%2. With appropriate therapy, risk is < 5%3. Risk factors for vertical transmission include maternal 3. Risk factors for vertical transmission include maternal viral load and degree of immunodeficiency and viral load and degree of immunodeficiency and PROM.PROM.

Human Immunodeficiency Virus (2)Human Immunodeficiency Virus (2)

Clinical manifestations :Clinical manifestations :1. 1. generally asymptomatic for first few months of life; generally asymptomatic for first few months of life; mean age of onset of symptoms is 1 year mean age of onset of symptoms is 1 year2. Common manifestations include failure to thrive,2. Common manifestations include failure to thrive, hepatosplenomegaly, oral candidiasis, recurrent hepatosplenomegaly, oral candidiasis, recurrent diarrhea, recurrent bacterial infections, and PCP diarrhea, recurrent bacterial infections, and PCP between 3-6 months of age. between 3-6 months of age.3. Anemia, neutropenia, and thrombocytopenia are 3. Anemia, neutropenia, and thrombocytopenia are common common

Possible organismsPossible organisms

Bacteria :Bacteria :Trepnema pallidum, MycobacteriumTrepnema pallidum, Mycobacterium tuberc tuberculosisulosis

Virus :Virus :Rubella, CMV, HSV, HIV, EnterovirusRubella, CMV, HSV, HIV, Enterovirus

Protozoa :Protozoa :Toxoplasma gondii, PlasmodiumToxoplasma gondii, Plasmodium

EnterovirusEnterovirus---NEONATAL INFECTIONS (1)---NEONATAL INFECTIONS (1) Enterovirus infection frequently is with coxsackieviruses B2–B5 and Enterovirus infection frequently is with coxsackieviruses B2–B5 and

echoviruses 6, 9, 11, and 19. echoviruses 6, 9, 11, and 19. Transmission via :Transmission via :

1. 1. verticallyvertically before, during, or after delivery before, during, or after delivery2. horizontally from other infected family members or by 2. horizontally from other infected family members or by transmission in hospital nurseries transmission in hospital nurseries (sporadic or epidemic).(sporadic or epidemic).

Infection in utero may be associated with placentitis, fetal demise, nInfection in utero may be associated with placentitis, fetal demise, neonatal illness, and, possibly, congenital anomalies. eonatal illness, and, possibly, congenital anomalies.

Neonatal infection is associated with a range of clinical manifestatioNeonatal infection is associated with a range of clinical manifestations :ns :--- asymptomatic --- asymptomatic (the majority) (the majority) --- benign febrile illness --- benign febrile illness --- severe multi-system diseases--- severe multi-system diseases

Most affected newborns are full-term and previously well; Most affected newborns are full-term and previously well; Maternal history often reveals a recent viral illness, including Maternal history often reveals a recent viral illness, including feverfever a a

nd, frequently, nd, frequently, abdominal pain. abdominal pain.

EnterovirusEnterovirus---NEONATAL INFECTIONS (2)---NEONATAL INFECTIONS (2)

Symptoms in the neonate may occur throughout the newborn period, with sSymptoms in the neonate may occur throughout the newborn period, with some ome beginning as early as day 1 of lifebeginning as early as day 1 of life; severe disease generally has an ons; severe disease generally has an onset within the first 2 wk of life. et within the first 2 wk of life.

Clinical manifestations :Clinical manifestations :------ fever fever or hypothermia, or hypothermia, irritability irritability, lethargy, anorexia,, lethargy, anorexia,------ rash rash (maculopapular, occasionally petechial or papulovesicular), (maculopapular, occasionally petechial or papulovesicular), jaundice, jaundice,--- respiratory symptoms, apnea, --- respiratory symptoms, apnea, hepatomegaly,hepatomegaly, abdominal abdominal distention, emesis, diarrhea, and decreased perfusion. distention, emesis, diarrhea, and decreased perfusion.

Most symptomatic neonates have benign courses, with resolution of fever iMost symptomatic neonates have benign courses, with resolution of fever in an average of 3 days and of other symptoms in about 1 wk. Occasionally, n an average of 3 days and of other symptoms in about 1 wk. Occasionally, a biphasic course may occur. a biphasic course may occur.

Laboratory findings: Laboratory findings: --- leukocytosis, --- leukocytosis, thrombocytopeniathrombocytopenia, pleocytosis, , pleocytosis, --- elevated transaminases and bilirubin, coagulopathy,--- elevated transaminases and bilirubin, coagulopathy,--- pulmonary infiltrates,--- pulmonary infiltrates,--- EKG changes.--- EKG changes.

EnterovirusEnterovirus---NEONATAL INFECTIONS (3)---NEONATAL INFECTIONS (3)

Complications include :Complications include :--- CNS necrosis and generalized or focal neurologic compromise--- CNS necrosis and generalized or focal neurologic compromise--- arrhythmias, congestive heart failure, myocardial infarction, and--- arrhythmias, congestive heart failure, myocardial infarction, and pericarditis; pericarditis; --- hepatic necrosis and failure; intracranial or other bleeding;--- hepatic necrosis and failure; intracranial or other bleeding;--- adrenal necrosis and hemorrhage; and rapidly progressive --- adrenal necrosis and hemorrhage; and rapidly progressive pneumonitis. pneumonitis. --- Myositis, NEC, SIADH, hemophagocytic syndrome, and sudden--- Myositis, NEC, SIADH, hemophagocytic syndrome, and sudden death are rare events. death are rare events.

Mortality in those with severe disease is significant and is most often Mortality in those with severe disease is significant and is most often associated with hepatitis and associated bleeding complications, myassociated with hepatitis and associated bleeding complications, myocarditis, or pneumonitis.ocarditis, or pneumonitis.

Risk factors for severe disease include :Risk factors for severe disease include :--- illness onset in the first few days of life, --- illness onset in the first few days of life, --- --- maternal illness just prior to or at deliverymaternal illness just prior to or at delivery, prematurity, male sex,, prematurity, male sex,--- infection by echovirus 11 or a coxsackie B virus, --- infection by echovirus 11 or a coxsackie B virus, --- positive serum viral culture, --- positive serum viral culture, --- absence of neutralizing antibody to the infecting virus, --- absence of neutralizing antibody to the infecting virus, --- evidence of severe hepatitis and/or multi-system disease.--- evidence of severe hepatitis and/or multi-system disease.

Congenital syphilis (1)Congenital syphilis (1) Transplacental transmission of Transplacental transmission of Treponema pallidumTreponema pallidum (spirochetes) (spirochetes) Transmission can occur at any stage of pregnancy; transmission rate aTransmission can occur at any stage of pregnancy; transmission rate a

pproaching 100%.pproaching 100%. Fetal and perinatal death occurs in 40% of affected infants.Fetal and perinatal death occurs in 40% of affected infants. Clinical manifestations :Clinical manifestations :

1.early signs : (during the first 2 yr of life)1.early signs : (during the first 2 yr of life) --- ---hepatosplenomegalyhepatosplenomegaly, jaundice, elevated liver enzymes; , jaundice, elevated liver enzymes; bile stasisbile stasis ---diffuse ---diffuse lymphadenopathylymphadenopathy ---Coombs negative hemolytic anemia; ---Coombs negative hemolytic anemia; thrombocytopeniathrombocytopenia ---osteochondritis ---osteochondritis (wrist, elbow,ankle & knee) and periostitis (long bone)(wrist, elbow,ankle & knee) and periostitis (long bone)

---mucocutaneous rash : maculopapular or bullous lesions, followed b ---mucocutaneous rash : maculopapular or bullous lesions, followed byy desquamation involving hands and feet desquamation involving hands and feet ---CNS abnormalities, failure to thrive, chorioretinitis, nephritis ---CNS abnormalities, failure to thrive, chorioretinitis, nephritis2.late signs: (appear gradually during the first 2 decades)2.late signs: (appear gradually during the first 2 decades) ---result primarily from chronic inflammation of bone, teeth and CNS. ---result primarily from chronic inflammation of bone, teeth and CNS. ---olympian brow, Higoumenakis sign, saber shins, Hutchinson teeth, ---olympian brow, Higoumenakis sign, saber shins, Hutchinson teeth, mulberry molars, saddle nose mulberry molars, saddle nose---Juvenile paresis, Juvenile tabes, Clutton joint---Juvenile paresis, Juvenile tabes, Clutton joint

Congenital syphilis (2)Congenital syphilis (2)

Diagnosis :Diagnosis :1. nontreponemal tests :1. nontreponemal tests : ---VDRL, RPR ---VDRL, RPR ---detect Ab against a cardiolipin-cholesterol-lecithin ---detect Ab against a cardiolipin-cholesterol-lecithin complex complex ---helpful in screening ---helpful in screening ---titers elevate when active and decline when treatment ---titers elevate when active and decline when treatment is adequate is adequate2. treponemal tests :2. treponemal tests : ---TPI, FTA-ABS, and MHA-TP ---TPI, FTA-ABS, and MHA-TP ---measure Ab specific to ---measure Ab specific to T. pallidumT. pallidum ---confirmatory testing of positive results from ---confirmatory testing of positive results from nontreponemal tests. nontreponemal tests.

MalariaMalaria Plasmodium protozoaPlasmodium protozoa ((Plasmodium ovale, Plasmodium vivax, Plasmodium malPlasmodium ovale, Plasmodium vivax, Plasmodium mal

ariae, Plasmodium falciparumariae, Plasmodium falciparum).). Transmitted through :Transmitted through :

1. an infected female 1. an infected female Anopheles Anopheles species mosquito. species mosquito. 2. blood transfusion 2. blood transfusion 3. congenitally between mother and fetus (rare)3. congenitally between mother and fetus (rare)

Clinical manifestations :Clinical manifestations :1. asymptomatic during the initial phase (incubation period)1. asymptomatic during the initial phase (incubation period)2. paroxysms of 2. paroxysms of feverfever, rigors, sweats, , rigors, sweats, headacheheadache, myalgia, back pain,, myalgia, back pain,

abdominal painabdominal pain, nausea, vomiting, diarrhea, pallor and, nausea, vomiting, diarrhea, pallor and jaundice jaundice.. Diagnosis :Diagnosis :

1. identification of organisms on Giemsa-stained smears of1. identification of organisms on Giemsa-stained smears of peripheral blood peripheral blood2. monoclonal antibody test2. monoclonal antibody test3. PCR3. PCR

Congenital malariaCongenital malaria Malaria acquired from the mother prenatally or perinatallMalaria acquired from the mother prenatally or perinatall

y.y. In endemic areas, congenital malaria is an important cauIn endemic areas, congenital malaria is an important cau

se of se of abortions, miscarriages, stillbirth, premature births, abortions, miscarriages, stillbirth, premature births, IUGR and neonatal deathsIUGR and neonatal deaths..

Congenital malaria usually occurs in a nonimmune mothCongenital malaria usually occurs in a nonimmune mother with er with P. vivaxP. vivax or or P. malariaeP. malariae, although it can be observ, although it can be observed with any of the human malaria species.ed with any of the human malaria species.

Symptoms and signs most commonly occurs between 1Symptoms and signs most commonly occurs between 10-30 days of age (14hr to several months of age)0-30 days of age (14hr to several months of age)

Clinical manifestations :Clinical manifestations :feverfever, restlessness, drowsiness, pallor, jaundice, poor fe, restlessness, drowsiness, pallor, jaundice, poor feeding, vomiting, diarrhea, cyanosis and eding, vomiting, diarrhea, cyanosis and hepatosplenomehepatosplenomegalygaly..

Mycobacteria infection (1)Mycobacteria infection (1) Mycobacterium tuberculosisMycobacterium tuberculosis complex : complex : M. tuberculosis, M bovis, M afriM. tuberculosis, M bovis, M afri

canum, M. microti, and M. canetticanum, M. microti, and M. canetti Transmission :Transmission :

1. person to person by airborne mucus droplet 1. person to person by airborne mucus droplet (most adults no longer(most adults no longer transmit the organism within several days to 2 wk after chemotherapy) transmit the organism within several days to 2 wk after chemotherapy)2. M. bovis may penetrate GI mucosa or invade lymphatic tissue of 2. M. bovis may penetrate GI mucosa or invade lymphatic tissue of oropharynx oropharynx (human infection is rare as a result of pasteurization of milk &(human infection is rare as a result of pasteurization of milk & effective TB control program for cattle) effective TB control program for cattle)

Pregnancy and the newborn :Pregnancy and the newborn :1.congenital tuberculosis is rare because the most common result of1.congenital tuberculosis is rare because the most common result of female genital tract tuberculosis is infertility. female genital tract tuberculosis is infertility.22.primary infection.primary infection just before or during pregnancy is more likely to just before or during pregnancy is more likely to cause congenital infection than is reactivation of a previous infection. cause congenital infection than is reactivation of a previous infection.

3.tubercle bacilli first reach fetal liver, then pass into fetal circulation3.tubercle bacilli first reach fetal liver, then pass into fetal circulation and infect many organs. and infect many organs.4.congenital tuberculosis may also be caused by 4.congenital tuberculosis may also be caused by aspiration oraspiration or ingestion of infected amniotic fluid. ingestion of infected amniotic fluid.

Mycobacteria infection (2)Mycobacteria infection (2)

Lymphohematogenous (disseminated) disease :Lymphohematogenous (disseminated) disease :

Tubercle bacilli are disseminated to distant sites, including Tubercle bacilli are disseminated to distant sites, including liver, spleen,skin and liver, spleen,skin and lung apiceslung apices, in all cases of tuberculosis infection. , in all cases of tuberculosis infection.

Lymphohematogenous spread is usually asymptomatic.Lymphohematogenous spread is usually asymptomatic. Clinical manifestations :Clinical manifestations :

------hepatomegaly, splenomegalyhepatomegaly, splenomegaly------lymphadenitis lymphadenitis in superficial or deep nodesin superficial or deep nodes------papulonecrotic tuberculidspapulonecrotic tuberculids appearing on the skin appearing on the skin---bone and joints or kidneys also may become involved---bone and joints or kidneys also may become involved---meningitis occurs only late in the course of the disease---meningitis occurs only late in the course of the disease

Miliary disease Miliary disease (the most clinically significant form of disseminated TB)(the most clinically significant form of disseminated TB)---occurs when massive numbers of tubercle bacilli are released into---occurs when massive numbers of tubercle bacilli are released into bloodstream, causing disease bloodstream, causing disease in two or more organs.in two or more organs.---occur within 2-6 mo of the initial infection---occur within 2-6 mo of the initial infection---lesions are often larger and more numerous in the lungs, spleen,---lesions are often larger and more numerous in the lungs, spleen, liver and bone marrow than other tissues. liver and bone marrow than other tissues.---chronic or recurrent headache (meningitis)---chronic or recurrent headache (meningitis)---abdominal pain or tenderness (tuberculous peritonitis)---abdominal pain or tenderness (tuberculous peritonitis)---cutaneous lesions ---cutaneous lesions papulonecrotic tuberculidspapulonecrotic tuberculids, nodules, or purpura., nodules, or purpura.

Mycobacteria infection (3)Mycobacteria infection (3) Tuberculous MeningitisTuberculous Meningitis

Tuberculosis of the CNS accounts for about 5% of extrapulmonary cases. It is seTuberculosis of the CNS accounts for about 5% of extrapulmonary cases. It is seen most often in young children but also develops in adults, especially those who en most often in young children but also develops in adults, especially those who are infected with HIV.are infected with HIV.

From hematogenous spread or rupture of a subependymal tubercle into the subarFrom hematogenous spread or rupture of a subependymal tubercle into the subarachnoid space .achnoid space .

may present subtly as may present subtly as headache headache and and mental changesmental changes or acutely as or acutely as confusion, lethconfusion, lethargyargy, , altered sensoriumaltered sensorium, and , and neck rigidityneck rigidity. .

Typically, the disease evolves over 1 or 2 weeks, a course longer than that of bacTypically, the disease evolves over 1 or 2 weeks, a course longer than that of bacterial meningitis; terial meningitis; Hydrocephalus is commonHydrocephalus is common . .

Lumbar puncture is the cornerstone of diagnosis. Lumbar puncture is the cornerstone of diagnosis. In general, CSF reveals a In general, CSF reveals a high leukocyte count, a protein content of 100 to 800 high leukocyte count, a protein content of 100 to 800

mg/dL, and a low glucose concentration.mg/dL, and a low glucose concentration. AFBAFB are seen on direct smear of CSF sediment in only 20% of cases, but repeate are seen on direct smear of CSF sediment in only 20% of cases, but repeate

d lumbar punctures increase the yield. Culture of CSF is diagnostic in up to 80% d lumbar punctures increase the yield. Culture of CSF is diagnostic in up to 80% of cases. of cases.

CTCT and and MRIMRI may show hydrocephalus and abnormal enhancement of basal ciste may show hydrocephalus and abnormal enhancement of basal cisterns or ependyma rns or ependyma

---Congenital tuberculosis------Congenital tuberculosis---

symptoms may be symptoms may be present at birthpresent at birth but more commonly begin by but more commonly begin by the 2nd or 3rd wk of life. the 2nd or 3rd wk of life.

clinical manifestations:clinical manifestations: respiratory distress, respiratory distress, fever,fever, hepatic or splenic enlargementhepatic or splenic enlargement, poor, poor feeding, lethargy or irritability, feeding, lethargy or irritability, lymphadenopathylymphadenopathy, abdominal, abdominal distention, failure to thrive, ear drainage, and distention, failure to thrive, ear drainage, and skin lesionsskin lesions..

Many infants have an Many infants have an abnormal chest radiographabnormal chest radiograph, most often a , most often a miliary pattermiliary patternn. .

Some with no pulmonary findings early in the course of the disease later deSome with no pulmonary findings early in the course of the disease later develop profound radiologic and clinical abnormalities.velop profound radiologic and clinical abnormalities.

Clinical presentation of TB in newborn is similar to that caused by bacterial sClinical presentation of TB in newborn is similar to that caused by bacterial sepsis and other congenital infection, such as syphilis, toxoplasmosis and Cepsis and other congenital infection, such as syphilis, toxoplasmosis and CMV.MV.

Diagnosis :Diagnosis :acid-fast stain of gastric aspirateacid-fast stain of gastric aspirate, middle-ear discharge, bone marrow, trach, middle-ear discharge, bone marrow, tracheal aspirate, or biopsy tissue (especially liver)eal aspirate, or biopsy tissue (especially liver)

ImpressionImpression

1.Mycobacteria tuberculosis1.Mycobacteria tuberculosis 2.Enterovirus infection2.Enterovirus infection

Diagnostic procedureDiagnostic procedure

AFB and culture of CSF from mother & gaAFB and culture of CSF from mother & gastric aspirate from neonatestric aspirate from neonate

PCR for enterovirusPCR for enterovirus

Thank you !!Thank you !!