Path 5 Flashcards
How many children are HIV +ve? (2012) How many of them are in Sub-Saharan Africa?
Total 3.3 Million
2.9 Million in SSA
What % of people living wit HIV are children? (2010)
1 in 10
How do children get HIV?
> 90% due to mother-child transmission
but also:
-child sexual abuse
- exchanging sex for food/shelter
What % of deaths under 5 in S-Africa are due to HIV?
~35%
Sx of HIV infection in children
- failure to thrive
- (chronic bilateral) parotid enlargement
- (drastic) lymphadenopathy
- rashes (molloscum, scabies (can even be not itchy b/c immune response is needed for itchiness)/ nappy rash
- herpes zoster infection
- hepato-/splenomegaly
- (severe) oral thrush
- TB/severe pneumonia/LIP/Pneumocystitis carinii
- recurrent/persistent diarrhoea
- clubbing
- CNS involvement (
LIP
lymphoid interstitial pneumonitis
(cannot be distinguished from TB on CXR)
CNS changes in children infected with HIV
Basal ganglia calcification
White matter changes
Atrophy
Vasculopathy / Strokes
How can HIV be transmitted from mother to child?
in utero
intra partum
breastfeeding
HIV - what is MTCT?
mother to child transmission
What is a major risk factor for HIV MTCT?
Maternal plasma viral load
What is the pattern of viraemia (with viral load numbers) in HIV infection in humans?
- rapid rise and initial peak at 10^6 copies/ml
- drop and set point at 10^3 - 10^5 copies/ml
- rise of copies/ml in late disease
Stats about risk of getting HIV via breast feeding?
- 4% transmission risk for every 6 months of breast-feeding
- risk of of HIV transmission must be balanced against risk of increased mortality from formula feeding
- Risk from drinking 1 litre of breast milk = risk from one episode of unprotected sex
- If IMR is > 40 / 1,000 live births, recommend exclusive breast feeding + ARVs for mother or baby [WHO 2010]
(this is about sub Saharan Africa )
What is IMR?
infant mortality rate
Approaches to prevent HIV infection in infants
- prevention of HIV in parents
- prevention of unintended pregnancies in HIV +ve women
- prevention of MTCT
- Care and support for HIV-infected women, their infants and their families
What classes of antiretrovirals are currently used in children with HIV in Africa?
- non-nucleoside reverse transcriptase inhibitors
- nucleoside analogues
- nucleotide analogues
- protease inhibitors
What medication group ends with -gravir?
integrase inhibitors
Name examples of integrase inhibitors
Raltegravir
Elvitegravir
Dolutegravir
When is Fontana Stain positive?
melanoma
What does a positive fontana strain indicate?
melanoma
When is Congo red stain positive? What birefringence is seen?
amyloidosis
+ apple green birefringence
What stain in +ve in amyloidosis?
Congo red + apple green birefringence
What stain is positive in Wilson’s disease?
Rhodanine (golden brown against blue counterstain)
+ve for copper
When is Rhodanine stain +ve? What colour does it change to?
Wilson’s disease
Golden brown against blue counterstain
(+ve for copper)
Prussian blue stain +ve - diagnosis?
Haemochromatosis
(+ve for iron)
Which stains are positive in haemochromatosis?
Prussian blue and Perl’s stain
(both are +ve for iron)
Perl’s stain +ve - diagnosis? What makes it +ve?
haemochromatosis
iron
Cytokeratin stain +ve - what is it?
positive for epithelial cells -> carcinoma
CD45 stain +ve - what is it?
+ve for lymphoid cells / lymphocytes
Ziehl Neelsen Stain +ve - diagnosis?
What colour change can be seen?
+ve for acid fast bacilli - TB
red against a blue background
Rhodamine-Auramine stain +ve - diagnosis and colour
TB
colour: bright yellow
What stains are +ve in TB
Ziehl Neelsen and Rhodamine-Auramine
What stain is positive in pneumocystitis jirovecii? What can be seen?
Gomori’s methanamine silver stain
flying saucer shaped cysts
Gomori’s methanamine silver stain with flying saucer shaped cysts - diganosis?
Pneumocystis jirovecii
What type of pathogen is Pneumocystis jirovecii?
fungus
What stain to test for cryptosporidium parvum?
Modified Kinyoung acid fast stain
Modified Kinyoung acid fast stain - diagnosis?
Cryptosporidium parvum
When is India ink stain +ve ? What can be seen?
Cryptococcus neoformans
(yeast cells surrounded by halos)
What stain is +ve in Cryptococcus neoformans and what can be seen?
India ink stain
(yeast cells surrounded by halos)
when is Giemsa stain +ve?
Chlamydia psittaci (cytoplasmic inclusions seen)
Which stain is +ve in Chlamydia psittaci and what can be seen?
Giemsa stain
(cytoplasmic inclusions seen)
Fite stain +ve - diagnosis?
Mycobacterium leprae
What stain is +ve in mycobacterium leprae?
What are the symptoms of Zika virus?
1 in 5 infected people have symptoms
- fever
- rash
- joint pain
- headache
- conjunctivitis
- muscle pain
Sx last for several days to a week
How can you get Zika virus?
- mosquito bite
- mother to child transmission in pregnancy
- sex
- blood transfusion
HOW does Zika virus cause damage in pregnancy?
- crosses the placenta
- targets neuronal progenitor cells (neuronal growth, proliferation, migration is disrupted)
What problems does Zika virus cause to the baby in pregnancy?
- microcephaly
- craniofacial disproportion
- skull abnormalities
- damage to the brain
- seizures
- problems with hearing (?SN hearing loss)
- problems with vision
- problems with feeding (issues swallowing)
- problems with moving limbs and body
Advice for women regarding Zika and pregnancy
- All travellers – bite avoidance
- Pregnant women – avoid travel to areas with current transmission
- Avoid conception for 2 – 6 months after travel (prolonged viral shedding in semen)
- Testing only if symptomatic or abnormalities identified on antenatal USS
Is a flare-up of genital herpes in pregnancy dangerous?
No
you have antibodies that protect you and the baby
only primary infections are worrying
What are the risks of primary HSV infection in pregnancy to the baby?
- miscarriage
- congenital abnormalities (ventriculomegaly, CNS abnormalities)
- preterm birth
What cancer does EBV infection predispose you to?
Burkitt’s lymphoma
What kind of virus is CMV?
enveloped
dsDNA genome
In which cells does CMV remain latent?
Lies latent in monocytes
and dendritic cells
which cells does EBV remain latent in?
B-cells
epithelial cells
NK cells
T-cells
What are the features of congenital varicella syndrome?
neurological abnormalities
ocular abnormalities (e.g. microphtalmia)
limb abnormalities
GI abnormalities
low birth weight
skin scarring
What are the risks to mum in VZV infection in preganncy
- 10-20% pregnant women are susceptible to VZV
- 10-20% pregnant women with varicella will have varicella pneumonia
- encephalitis (Rare, but 5-10% cases are fatal)
- pregnant women are 5x more likely to develop varicella pneumonitis compared to the general population
What is the risk of baby developing congenital varicella syndrome at different points in the pregnancy
0.4% if maternal infection weeks 0-12
2% if weeks 12-20
studies have not shown cases after 28w
management of varicella zoster exposure in pregnancy
if immunity status is unknown, CHECK FOR ANTIBODIES FIRST
If no antibodies
<20 w give VZIG asap
> 20 w give oral antivirals (acyclovir or valacyclovir) for days 7-14 post exposure
management of chickenpox in pregnancy
- seek specialist advice
- ≥ 20 weeks and she presents within 24 hours of onset of the rash - give oral acyclovir
- if < 20 weeks the aciclovir should be ‘considered with caution’
RCOG guidelines
How long should PTSD sx be present for to make the diagnosis?
4w
or 1 month
Causes of microcytic anaemia
- iron deficiency
- anaemia of chronic disease
- sideroblastic anaemia
- beta thalassemia
What is sideroblastic anaemia?
Ineffective erythropoiesis → the body produces enough iron but is unable to effectively put it in RBCs. Iron loading (bone marrow) causes haemosiderosis (endocrine, liver and cardiac damage due to iron deposition)
How are lithium levels monitored?
once weekly in the beginning
once settled: every 3 months.
Lithium levels should be measured 12h after taking the medication
CHESS organisms
-> cause bloody diarrhoea
C - campylobacter
H - Hemorrhagic E. coli (O157:H7)
E - Entamoeba histolytica
S - salmonella
S - shigella
What are the different types of HSV infection in neonates?
SEM (skin, eye, mouth disease)
- 45% cases
- initially benign, high risk of progression to CNS
- must be treated (acyclovir)
- usually first 14 days, up to 16w
CNS (+/- SEM)
- 30% cases
- weeks 203 of life (up to 6)
- Sx: seizures, lethargy, irritability, poor feeding, fevers - need CSF
Disseminated
- presents like sepsis
- often in 1st week of life
- multi organ involvement (liver, lungs, CNS, heart, GIT, renal tract, BM)
How do you manage HSV in pregnancy?
aciclovir (can be used in any trimester)
if primary HSV in 3rd TM recommend C/S
What is in-utero HSV infection?
very rare but severe
baby gets HSV in utero from mother with primary infection
Risks:
Primary infection only
Miscarriage
Congenital abnormalities ( ventriculomegaly, CNS abnormalities)
Preterm birth
IUGR
Risks of varicella in pregnancy to the baby
Congenital Varicella syndrome
- skin scarring
- neurological abnormalities
- ocular abnormalities
- low birth weight
- limb abnormalities
- GI abnormalities
Risks of varicella in pregnancy to the mum
- 10-20% pregnant women susceptible
- 5x higher risk of VZV pneumonia than gen pop (10-20% pregnant women with VZV will get this)
- VZV encephalitis is rare but severe
if presenting with exposure/sx -> check immunity status and measure antibodies
Management of VZV exposure and infection in pregnancy
Exposure: if hx of infection or 2 vaccinations -> sufficient evidence of immunity; otherwise measure VZV IgG in blood; if VZV IgG <100 mIU/ml offer PEP
PEP: aciclovir or valaciclovir
Infection: treat with aciclovir
How high is the risk of transmitting VZV to baby in pregnancy?
0.4% if maternal infection weeks 0-12
2% if weeks 12-20
20+ weeks: ?????????
What antibody is checked for VZV immunity and what is the cut off level?
VZV IgG
<100 mIU/ml -> offer PEP
What % women are susceptible to CMV? How many of them will become infected with CMV in pregnancy? How many of them will transmit it to baby?
50 % susceptible
1% of them will develop infection in pregnancy
40% babies will get it
what % babies exposed to CMV in pregnancy will develop sx?
5% have clinical issues at birth, e.g. hepatosplenomegaly, petechia, most of them will have neurodevelopment disabilities later in life e.g. SN hearing loss, CP, epilepsy, cognitive impairment
5% develop issues later in later, mainly SN hearing loss
90 % normal at birth and normal development
When are the greatest risks with rubella infection in pregnancy
1st TM
What are the risks with rubella infection at different times in pregnancy?
before 8 weeks -> 20% spont abortion
before 10 weeks 90% incidence of fetal defects
after 18-18 weeks -> hearing defects and retinopathy
after 20 weeks risk is much lower
How is rubella spread to baby in pregnancy?
via the placenta
congenital rubella syndrome
Early manifestations:
- Bone lesions
- Microcephaly
- Cataracts
- Retinopathy
- Meningoencephalitis
- congenital cardiac disease (PDA, PS)
- Purpura
- Hepatosplenomegaly
Late onset manifestations
- Hearing loss
- Intellectual disability
- Panencephalitis
- DM
- Thyroid dysfunction
Rubella viraemia post birth - problem?
yes, it continues to damage the infant
How do rubella and measles rashes spread?
rubella: starts on face, spreads to trunk
measles: starts at hairline/behind ears, spreads cephalocaudally over 3 days `
What type of virus is rubella?
Togavirus
What type of virus is measles
Paramyxovirus – RNA virus
How Is measles transmitted?
respiratory (isolate!)
conjunctiva
How is rubella transmitted?
respiratory (isolate!)
Fetal risks with Rubella
Congenital rubella syndrome
Early manifestations:
- Bone lesions
- Microcephaly
- Cataracts
- Retinopathy
- Meningoencephalitis
- Congenital heart disease(PDA, PS)
- Purpura
- Hepatosplenomegaly
Late onset manifestations
- Hearing loss
- Intellectual disability
- Panencephalitis
- DM
- Thyroid dysfunction
Maternal sx and risks with measles infection
Measles sx:
- Prodrome 2-4 days
- Conjunctivitis
- Koplick spots
- Rash
Complications for mother:
- Secondary bacterial infection
- Otitis media / pneumonia / GI
- encephalitis
Fetal risks of maternal measles infeciton
- foetal loss,
- preterm delivery
- no congentila abnormalities
- SSPE (subacute sclerosing panencephalitis – fatal, progressive disease of the CNS, occurs 7-10 years after natural infection
What is SSPE?
subacute sclerosing panencephalitis
fatal, progressive disease of the CNS
occurs 7-10 years after natural infection with measles
possible complication of measles in pregnancy
Parvovirus transmission
respiratory and blood products
what proportion of adults have parvovirus antibodies?
30-60%
Parvovirus dx
Virus detection (PCR)
Serology
Rubella dx
Virus detection (PCR)
Serology
CMV dx
PCR of urine/saliva/amniotic fluid/tissue
Serology
HSV dx
viral detection - lesion swab for PCR
serology
Sx of parvovirus in pregnancy
- Mostly asymptomatic
- Erythema infectiosum/ slapped cheek/5ths disease
- Polyarthropathy
- Transient aplastic crisis
When are you infectious with parvovirus?
6d post exposure - 1 week (infectious before sx commence)
Risks to fetus in parvovirus infection in pregnancy
Before 20 weeks
* Transmission 33%
* 9% risk of infection
* 3% hydrops fetalis if infection)
* 1% fetal anomalies
* 7% fetal loss
Refer to FMU, may require intrauterine transfusion
No documented risks after 20 weeks
What is hydrops fetalis?
Fetal hydrops
Cytotoxic to fetal red blood precursor cells
-> anaemia
-> accumulation of fluid in soft tissues and serous cavities.
-> can rapidly cause fetal death
Which enterovirus poses the main risk in pregnancy? How?
Coxsackie
Perinatal newborn infection can occur in last week of pregnancy
Neonates are at risk of myocarditis, fulminant hepatitis, encephalitis , bleeding and MOF.
questions to ask pregnanct woman presenting with rash
- Gestation
- Date of onset, clinical features, type and distribution of rash, associated features
- Past relevant history of infection
- Past relevant history of antibody testing
- Past immunisation history (and dates/places)
- unwell contacts
- Travel history
advice for women traveling to zika endemic areas
- avoid conception for 2-6 months after travel (prolonged viral shedding in semen)
- avoid travel to endemic areas in pregnancy
What % of babies born to people with Zika while pregnant will develop the typical abnormalities
5%
What organisms cause PID secondary to abortion?
staph, strep, coliform bacteria, clostridium perfringens
usually start form the uterus and spread by lymphatics and blood vessels upwards, deep tissue layer involvement
What does CIN stand for?
cervical intraepithelial neoplasia
RFs for cervical cancer
Human Papilloma Virus -present in 95%
Many sexual partners
Sexually active early
Smoking
Immunosuppressive disorders
Cervix: what is the SCJ?
squamocolumnar junction
between the columnar epithelium and the transformation zone
Why has the incidence of cervical cancer declined?
Papanicolaou-test screening (Pap smear) and human papillomavirus (HPV) vaccination
What does Pap smear stand for?
Papanicolaou-test screening
What is CIN grading dependent on?
degree of atypia on cytology
Sx of cervical cancer
Patients are usually asymptomatic in the early stages and develop symptoms later in the course of the disease.
Early symptoms
Abnormal vaginal bleeding: irregular vaginal bleeding, heavy, irregular menstrual bleeding, postcoital spotting
Abnormal vaginal discharge: blood-stained or purulent malodorous discharge (not necessarily accompanied by pruritus)
Dyspareunia
Pelvic pain
Late symptoms: hydronephrosis, lymphedema, fistula formation
Cervical examination: ulceration, induration, or an exophytic tumor
What are the types of cervical cancer you can get, how common are they and what virus are they associated with
Squamous cell carcinoma - 80% - HPV 16
Adenocarcinoma - 20% - HPV 18
Small Cell Carcinoma - 2% - neuroendocrine tumour
What stages of HPV infection are there
latent/non-productive: HPV continues to reside in the basal cell, infectious visions are NOT produced, viral DNA replication is coupled to epithelial cell replication. complete viral particles are not produced. no cellular effects seen. infection can only be identified with molecular methods.
-> leads to immune response and regression
productive: viral DNA replication occurs independent of host chromosomal DNA synthesis. Large number of viral DNA are produced and result in infectious visions. characteristic histological and cytological features are seen.
-> can lead to malignant cells.
How does HPV transform cells?
encodes proteins E6 and E7
these bind to and inavtivate two tumour suppressor genes:
- p53 (E6)
- Retinoblastoma (Rb) gene protein (E7)
both interfere with apoptosis and increase unscheduled cellular proliferation both of which contribute to oncogenesis.
How does HPV transform cells?
encodes proteins E6 (mainly HPV and E7 mainly HPV (
these bind to and inavtivate two tumour suppressor genes:
- p53 (E6)
- Retinoblastoma (Rb) gene protein (E7)
both interfere with apoptosis and increase unscheduled cellular proliferation both of which contribute to oncogenesis.
What happens usually with HPV infection? What can happen?
Mostly:
nothing happens, body eliminates the infection.
HPV becomes undetectable in 2 y
relatively few develop symptoms
Persisten infection with high risk HPV types is associated with pre-cancerous and cancerous cervical changes.
Sensitivity of cervical cytology
50-95%
specificity of cervical cytology
90%
How is HPV tested for on cytology?
molecular genetic approaches.
HPV DNA test (nucleic acid solution hybridisation assay with signal amplification that uses long synthetic RNA probes complementary to low risk HPV types 6, 11, 42, 43 and 44 as well as high risk types 16, 18, 31, 33, 35, 39, 45, 51, 56, 58, 59, 68)
Which mutation affects >50% endeometriod cancers of the uterus?
PTEN
Which mutation affects >50% endeometriod cancers of the uterus?
PTEN
What is the commonest uterine tumour?
leiomyoma
p53, P13KCA, Her-2 amplification in endometrial biopsy - which cancer type?
endometrial serous carcinoma
Which mutations present in 90% endometrial serous carcinoma?
p53
Which mutations are seen in clear cell carcinoma?
PTEN
CTNNB1
Her-2 amplification
What are the risk factors for ovarian torsion?
ovarian mass (e.g. cyst or cancer)
ovary >5cm
Ultrasound findings in ovarian torsion
- whirlpool sign
- one ovary is larger than the other (due to oedema and blood pooling)
- decreased or absent blood flow
Mx of ovarian torsion
- urgent surgical detorsion (to avoid ischaemia and loss of the ovary and tube)
- unilateral sapling oophorectomy if ovary cannot be saved
Emergency adnexal masses
- ovarian torsion
- ruptured ovarian cyst
- tubo ovarian abscess
- ectopic pregnancy
ruptured ovarian cyst sx
sudden onset pain
either spontaneous or e.g. during sex or exercise
Mx of ruptured ovarian cyst
Minor bleeding
-> hameodynamic status and Hb not affected
-> treat with NSAIDs
-> sx should resolve in a few days.
Major bleeding
- present with peritoneal irritation e.g. guarding, tenderness
- USS shows blood in cavity
- admit and give IV fluids
- surgery may be needed to stop bleeding and remove the cyst
Sx of tuboovarian abcess
- acute lower abdo pain
- fever
- chills
- vaginal discharge
- mass is tender and painful
- high WCC
- USS shows complex mass that obliterates normal architecture.
Mx of tube-ovarian abscess
- admit urgently
- abx
- may need surgery
Mx of tube-ovarian abscess
- admit urgently
- abx
- may need surgery
USS findings in simple ovarian cysts
<10 cm
thin, regular walls
ulilocular
filled with anechoic fluid (homogenous)
-> benign
