Transcript Infant Diagnosis

Diagnosis of HIV in Infants
and Children
Learning Objectives
This presentation will:
Review key concepts in diagnosing HIV infection in
infants and young children
Review virologic and antibody tests
Explain the Ethiopian algorithms for diagnosing HIV in
infants and young children
Describe the use of clinical criteria to identify presumed
severe HIV-infection
Review roles of the parent and multidisciplinary team
2
Goal of Early Infant Diagnosis
 The primary goal of early infant diagnosis is to
identify the HIV-infected child early, prior to
the development of clinical disease during the
first months of life. The goal is NOT to exclude
infection in infants.
 Diagnosis should be early enough so interventions and
treatment can be started
 To reduce pediatric mortality and morbidity
 To initiate ART in an infant with rapidly progressing HIVdisease
3
It is important to remember
 Babies can acquire HIV infection during:
Pregnancy

Labor & delivery
Breastfeeding
Keeping this in mind will help you to understand infant
diagnosis
4
Complexities of Infant Diagnosis
 HIV infection is difficult to diagnosis in infants:
 Routine HIV antibody tests cannot be used
 Specialized virologic tests are necessary
 Clinical diagnosis requires frequent and close followup of the infant
 HIV infection is difficult to exclude in infants:
 Infants who breastfeed continue to be at risk for
acquiring HIV infection
• Risk of infection continues throughout duration of breast
feeding
• Diagnosis of infants is an ongoing process and depends on
good clinical reasoning as well as laboratory results
5
Complexities of HIV Diagnosis:
Antibody Testing
 All infants born to HIV+ mothers will test HIV antibody
positive in the first several months of life
 Maternal HIV antibody (IgG) is transferred across the placenta
during pregnancy
 A positive HIV antibody test in infants <18 months of age
will not distinguish whether or not the infant is HIVinfected; rather it shows that:
 Mother is HIV-infected
 Infant is at risk for HIV infection (exposed to HIV)
 If the child is not infected the HIV antibody fades during
first 6 - 18 months of life
 Most uninfected infants test negative by 12 months of age
 All uninfected infants test negative by 18 months of age
6
Antibody Detection in 77 HIV-Exposed,
Uninfected Infants in South Africa
100
90
80
70
60
% antibody 50
positive
40
30
20
10
0
Rapid Ab can be used
to exclude infection
around 12-18 months
of age
birth
Moodley D, PIDJ 1995;14:850
1
3
6
9
12
15
18
months of life
7
Complexities of HIV Diagnosis:
Virologic Tests
 Specialized virologic tests must be used




HIV DNA PCR
HIV RNA PCR
p24 Antigen
Viral Culture
 Two positive virologic tests = HIV infection
 One positive virologic test = Presumed HIV
infection
8
HIV DNA PCR
 HIV DNA PCR is a special laboratory test that
detects pieces of the viral gene that are
incorporated in the human blood cell
 By comparison, HIV Antibody testing detects the
antibody that the body makes in response to the
HIV virus
 Sensitivity of HIV DNA PCR increases with
time during the first month of life
 The infant may have HIV infection but there may
not be enough virus in the blood to detect it at
birth. It becomes easier to find/detect as the infant
gets a little older
9
DNA PCR for Infant Diagnosis
100
90
80
70
60
sensitivity % 50
40
30
20
10
0
At 4-6 weeks of age
sensitivity of
DNA PCR is 9698%
48 hrs
2-7 days
7-14 days
28 days
days
Dunn D, AIDS 1995, 9:F7
10
Complexities of HIV Diagnosis:
Breastfed infants
 Breastfed infants
 Remain at risk for acquiring HIV infection throughout
the duration of breastfeeding
 Most are infected in utero, intrapartum and early
postpartum (by 6 weeks of age)
 A negative virologic test cannot reliably exclude HIV if
the infant is still breastfeeding
 Infant must always be tested again 6-12 weeks after
complete cessation of breastfeeding
11
How to Approach Diagnosis of HIV
Infection in Children < 18mo
1. Know that the child is at risk for HIV
infection
•
•
Born to an HIV-infected woman
Tests HIV-antibody positive
2. Pay close attention to the child’s clinical
status and growth pattern
3. Use special virologic tests to identify the
infected child, not to exclude infection in the exposed
child
4. Interpretation of virologic test results should
ALWAYS be done in the context of the clinical
presentation of the infant
12
How to Use Virologic Testing
 Every HIV-exposed baby should have
a DNA PCR test
At 4-6 weeks of life
or
At first visit* (if >6 weeks of age)
*If the child presents at 9-18 months of age
screen with a rapid antibody first
13
Diagnosing a Child Who Presents at 9-18
Months of Age
 Asymptomatic child
Screen with HIV antibody
 If positive, virologic testing is indicated
 If negative, no virologic testing is necessary
• If breastfeeding, repeat antibody testing >6-12 weeks
after cessation of breastfeeding
 Symptomatic child
Screen with virologic testing
14
What if the DNA PCR is Positive?
If the HIV DNA PCR result is
POSITIVE
the baby is presumed to be
HIV-INFECTED
15
What if the DNA PCR is Positive?
 Refer the baby for HIV care &
treatment
Don’t wait!
 Start or continue cotrimoxazole
 Continue exclusive breastfeeding
(EBF) through 6 months of age
16
What should you tell the care giver if the
initial PCR test is Positive?
 HIV has been detected in your infant’s blood
 This means that your child has HIV infection
 We will check your baby carefully and refer you
and your baby to a clinic where there are
doctors and nurses who are experts in taking
care of children with HIV
 The doctors and nurses will teach you how to
care for yourself and the baby so you both stay
healthy
17
Diagnostic Algorithm for Infants
< 18 months of age
Infant 4-6 weeks of age
or at first clinic visit#
HIV DNA PCR
HIV DNA PCR POSITIVE
Presumed HIV-INFECTED
# Confirm HIV exposure with Rapid Antibody
test if > 9 months of age. If antibody
negative, and infant is still breastfeeding,
repeat Rapid Antibody test >6-12 weeks
after complete cessation of breast feeding.
•Do not WAIT. Refer for HIV care
& treatment IMMEDIATELY
•Start/continue cotrimoxazole
prophylaxis
18
What if the DNA PCR is Negative?
If the HIV DNA PCR result is
NEGATIVE
the baby is presumed NOT to be
HIV-infected
NOTE: Infants who are still breastfeeding are at
continued risk for acquiring HIV infection
19
What if the DNA PCR is Negative?
 Continue follow-up
 Continue cotrimoxazole (CTX)
 Continue exclusive breastfeeding (EBF)
through 6 months of age
20
What should you tell the care giver if
the initial PCR test is Negative?
 We did not find the HIV virus in your baby’s blood
 Since you are breastfeeding, your baby may still get the
virus from the breast milk
 We will have to keep checking on him/her and look for
the virus until 6 weeks after s/he stops breastfeeding
 If he or she stays well, we will not test again until at least
6 weeks after you wean the baby from the breast
 If your baby gets get sick, we will repeat the special test
again to check for the virus
 You need to keep bringing your child for check ups and
continue cotrimoxazole
21
Diagnostic Algorithm for Infants
< 18 months of age
Infant 4-6 weeks of age
Or at first clinic visit
HIV DNA PCR
HIV DNA PCR POSITIVE
HIV-INFECTED
•Do not WAIT. Refer for HIV care
& treatment IMMEDIATELY
•Start/continue cotrimoxazole
prophylaxis
DNA PCR NEGATIVE
Continue CTX and clinical follow-up
22
What if the Initial DNA PCR is
Negative and the child is WELL?
Repeat HIV testing 6-12 weeks after
weaning using
Rapid HIV Antibody Test
NOTE: Breastfeeding babies remain at risk for
acquiring HIV
23
Diagnostic Algorithm for Infants
< 18 months of age
Infant 4-6 weeks of age
Or at first clinic visit
HIV DNA PCR
HIV DNA PCR POSITIVE
HIV-INFECTED
•Do not WAIT. Refer for HIV care &
treatment IMMEDIATELY
•Start/continue cotrimoxazole
prophylaxis
DNA PCR NEGATIVE
Continue CTX and close follow-up
WELL Infant
HIV Rapid Antibody
at ≥ 12 months of age
and or >6-12 weeks after
weaning
24
What if the HIV Antibody is
Negative?
If the HIV Antibody result is
NEGATIVE
the baby is presumed NOT to be HIVinfected
NOTE: At this point, the baby may be discharged from
the program
25
What if the HIV Antibody is Positive?
If the HIV antibody result is Positive
and the baby is > 18 (older than)
months of age the baby is
presumed to be
HIV-INFECTED
Refer for HIV care and treatment
26
What if the HIV Antibody is Positive?
If the HIV antibody is positive and
the baby is <18 (younger than)
months of age*
Repeat HIV DNA PCR
NOTE: Maternal antibody can persist until 18 months of
age
27
Diagnostic Algorithm for Infants < 18
months of age
Infant 4-6 weeks of age*
Or at first clinic visit
HIV DNA PCR
HIV DNA PCR POSITIVE
HIV-INFECTED
DNA PCR NEGATIVE
Continue CTX and clinical follow-up
•Do not WAIT. Refer for HIV
care & treatment
IMMEDIATELY
•Start/continue cotrimoxazole
prophylaxis
WELL Infant
HIV Rapid Antibody
at ≥ 12 months of age and or >612 weeks after weaning
HIV Antibody Positive@
HIV DNA PCR
@
Positive HIV Antibody diagnoses HIV infection if > 18mo at time
of weaning; It is not necessary to test with DNA PCR
HIV Antibody Negative
UNINFECTED
Discharge from
program
28
What if the Initial DNA PCR is Negative
but the child is ILL?
If the HIV DNA result is negative, but the child
develops HIV symptoms
•
•
•
•
•
Oral thrush
Pneumonia
Poor growth
Developmental delay
Chronic diarrhea
REPEAT HIV DNA PCR TESTING
NOTE: Breastfeeding babies remain at risk for acquiring
HIV
29
Diagnostic Algorithm for Infants
< 18 months of age
Infant 4-6 weeks of age
or at first clinic visit
HIV DNA PCR
HIV DNA PCR POSITIVE
HIV-INFECTED
DNA PCR NEGATIVE
Continue CTX and clinical follow-up
•Do not WAIT. Refer for HIV care
& treatment IMMEDIATELY
•Start/continue cotrimoxazole
prophylaxis
ILL Infant
Repeat
DNA PCR
WELL Infant
HIV Rapid Antibody
at ≥ 12 months of age
and or >6-12 weeks after
weaning
30
Summary: How to Use DNA PCR
Testing
 Every HIV-exposed baby should have a DNA
PCR test
 At 4-6 weeks of life* or at first visit if > 6
weeks of age#
 Any infant with an initial negative DNA PCR who
develops signs and symptoms of HIV infection
 Testing prior to 4 weeks in HIV-exposed infant
who is symptomatic
 In a baby < 18 mo who tests antibody positive
6 weeks after weaning
35
Summary: How to Use DNA PCR
Testing
As Ethiopia has adopted to use single positive
DNA PCR test result to enroll HIV exposed
infants into HIV care/ART all such infants must
have a confirmatory rapid antibody test at 18
months of age
36
Summary: When should you repeat
the DNA PCR?
 HIV antibody positive infant < 18 months of age
with signs and symptoms of HIV infection
 Children < 18 months of age with a positive
rapid antibody test > 6 weeks post-weaning
 A sick infant whose initial DNA PCR result
comes as negative
 An infant who becomes symptomatic after an
initial negative DNA PCR result
37
If the Child is <18 months and Virologic
Tests are not Available
 A presumptive diagnosis of HIV infection must
be made based on clinical findings
 Good clinical reasoning can identify children at high
risk for HIV disease & rapid progression
 The purpose of making a presumptive diagnosis
is to initiate ART in the sick child
 Infants with severe manifestations of HIV infection
should not be denied treatment because their
diagnosis cannot be confirmed
38
Presumptive Diagnosis of Severe
HIV Disease in Children <18 months
 HIV antibody positive and
 Diagnosis of Stage 4 or AIDS-indicator condition (s)

OR
 Symptomatic with ≥ 2 of the following:
• Oral thrush
• Severe pneumonia
• Severe sepsis
 Supporting factors
 Recent maternal death
 Advanced HIV disease in the mother
 CD4% < 25% in infant
 The diagnosis should be confirmed with HIV antibody
when the child reaches 18 months
39
Diagnosing HIV in the Child >18 Months
 HIV antibody should be used to diagnose HIV
infection in children > 18 months of age
 Children >18 months with positive antibody test
have HIV infection
 A positive antibody test should be confirmed by
duplicate testing
 A negative antibody test in children > 18 months
excludes HIV infection
 Except in cases of continued breast feeding.
Antibody should be repeated 6-12 weeks post
cessation of breast feeding
40
Diagnostic Algorithm for Children
> 18 months of age
Child > 18 months of age*
Rapid HIV Antibody Test
HIV Antibody NEGATIVE
HIV Antibody POSITIVE
HIV-INFECTED
Refer for HIV care &
treatment
Non-breast feeding child
UNINFECTED
Breast feeding child
remains at risk of infection
Repeat HIV Rapid Antibody
>6-12 weeks after weaning (after
6months of EBF)
HIV Antibody POSITIVE
HIV-INFECTED
Refer for HIV care &
treatment
HIV Antibody NEGATIVE
UNINFECTED
41
Summary: When should you use HIV
Antibody Tests?
 Children < 18 months of age
 Determine HIV exposure in infants born to women of
unknown HIV status
 Exclude infection in an infant who is not breastfed or
> 6 weeks post-weaning
 Exclude HIV infection in children > 9 months of age
 Children > 18 months of age
 Confirm HIV infection
42
Early and Frequent Clinical
Evaluation
 Close monitoring of growth and development
 Early identification of disease signs & symptoms
• Use of symptom checklist, monitor growth and
development closely
• Listen to the parent
• Common illnesses can mimic symptoms of HIVinfection (growth failure, recurrent fevers, diarrheal
illnesses)
 Cotrimoxazole prophylaxis for all HIV-exposed infants
until HIV has been excluded
 Vaccinations, per local guidelines
43
Critical Elements for Early Infant
Diagnosis
Remember
 Virologic tests should always be interpreted in
the context of the clinical presentation of the
child.
 Use your clinical judgment
 Don’t hesitate to question the results if they don’t
make sense. Errors do occur!
•
•
•
•
Are results valid?
Do the results make sense given the child’s health?
Is there a laboratory problem?
Could there be a specimen mix-up?
44
Critical Elements for Early Infant
Diagnosis (2)
 Early and frequent clinical evaluations
 Good Clinical Reasoning can identify children at
high risk for HIV disease & rapid progression during
the first months of life
 Early virologic testing
 Good communication with family is critical:
 Team members should emphasize importance of:
•
•
•
•
Determining HIV status
Adherence to visit schedule
Identifying signs and symptoms
Administering Cotrimoxazole prophylaxis
45
Critical Elements for Early Infant
Diagnosis (3)
 Children who have early virologic testing must
return to the clinic for results
 Both infants with positive and negative results
 Infants who are breastfeeding must be retained
in care until they are weaned and a final
infection status is determined
 Infant and children who are identified as HIVinfected will need to be linked to pediatric HIV
care and treatment service
46
Programmatic Barriers
 When an infant is seen at a maternal child health clinic
(or other site of care), how will the clinician know that
s/he is HIV-exposed?
 Coordination between the ANC, MCH, and CTC
 Use of rapid antibody to identify mothers and exposed infants if
maternal HIV status is not known
 Routine testing of children of adults in HIV care and treatment
programs
 Infants are not coming back for results






Use appointment systems
Monitor missed appointments
Enhance parent education
Reminders for parents and care givers
Active outreach after missed visits
Family education and support
47
Multidisciplinary Team
 Provide ongoing education, support, and
counseling to parent
 Identify problems and issues EARLY
 Form a bridge between parent and medical
provider
 Provide adherence support for both mother and
infant
 Introduce concept of infant diagnostic testing as
part of PMTCT program
48
Multidisciplinary Team (2)
 Support the decision to have early infant
diagnostic testing
 Review results of virologic test
 Explain implications
 Explore parental understanding
 Explore parental concerns
 Review infant feeding decisions
 Emphasize need for ongoing care and treatment
as determined by results
49
Role of the Parent/caregiver
 Parent needs to understand:
 That infant diagnosis is an ongoing process
 The importance of early testing, frequent monitoring,
and adherence to care
 Often the first to notice signs and symptoms
 Often has multiple complex roles and needs,
including self-care, caretaker role for other
family members, feelings about transmission of
HIV to the infant
 Parent needs understanding and support
50
Summary
 Clinical reasoning is critical to diagnosing infants with
HIV
 Early virologic testing should be used to identify the
infected infant at highest risk for disease progression
 Specialized virologic tests are used to diagnose HIV
infection in a child < 18 months
 Virologic tests may be unreliable or unavailable,
highlighting the importance of clinical evaluation
 The multidisciplinary team has numerous critical roles in
this process
 The parent or caretaker is the key player, and must be
educated and supported on this logistically, emotionally,
socially and medically complicated path
51
Case Study: Meseret
 6 week old infant, Meseret, is brought to clinic
for her first post-partum visit
 Mom delivered in a village outside of the city
where her mother and sister still live
 She just returned home with Meseret and her 4
year old son
 Mom was enrolled in a PMTCT program during
pregnancy
 What would you like to know about the baby and
his family?
52
Case Study: Meseret (2)
 Meseret was born at home without problems
 Mother doesn’t know birth weight, but brought
Meseret to health station at 4 days of age,
weighing 3 kg
 Mom took her sd-NVP, but the baby didn’t
receive any medication. Mom didn’t tell anyone
at home about her status
 Breastfeeding primarily but left the baby with her
sisters on two occasions. During that time
Meseret was fed water and maybe some milk
53
Case Study: Meseret (3)
 Dad is away working. Mom has not disclosed
her HIV status to him
 He comes home 1X/month and gives her money
but she must work in the fields and sells produce
to have enough money
 She uses the general water tap in the
neighborhood
 No running water in the house
 What will you do next?
 What is usually done at a baby’s first visit?
54
Case Study: Meseret (4)—Pertinent
Physical Exam
 Physical examination is remarkable for fairly
extensive oral thrush, and diffuse
lymphadenopathy
 The baby looks a little scrawny and seems
irritable
 What is your assessment of the child?
 What could be causing Meseret’s poor growth?
55
Meseret (5): Growth Chart for Infant Girl
Weight
Birth- 3kg
6 wks- 3.4 kg
56
Case Study: Clinical Questions
 Physical examination is remarkable for fairly
extensive oral thrush, and diffuse
lymphadenopathy
 The baby looks a little scrawny and seems
irritable
57
Case Study: Meseret (6)
 Mom reports that the baby has not been feeding well for
several days
 You watch the child feed but she tires quickly and falls
asleep. Mom says that this is what has been happening
over the last several days
 She also reports occasional watery stools
 She says that she had a ‘TB’ test at ANC and it was
negative
 Her mother (the child’s grandmother) seemed to be
coughing and had lost some weight, but she didn’t seem
to be too sick
58
Case Study: Meseret (7)
 You send blood for HIV DNA PCR
 You work with mom around enhancing feeding and
arrange for the family to receive food packages
 You prescribe nystatin for the oral thrush
 The child also begins cotrimoxazole prophylaxis
 Mom is instructed to come back in one week to check
the baby again
 Mom does not make the appointment the following week.
 What will the team do to address this missed visit?
59
Case Study: Meseret (8)—MDT
 The case is discussed at the weekly
multidisciplinary meeting and it is decided that
the mom should be contacted immediately. Her
cell number is no longer connected so the
decision is made to make a home visit
 A peer educator and a counselor travel to the
listed address. Mom is not at home but they find
the baby with a neighbor. Meseret seems sick
and has loud breathing
 What should they do?
60
Case Study: Meseret (9)
 Mom is due to return in a short time. She
usually comes home late morning to feed the
baby
 When she arrives you escort her to the clinic
with the baby
 Meseret is brought in to the nurse who weighs
her. Breathing seems fine now, but the child
weighs the same as last visit
61
Meseret -Growth Chart for Infant Girl
Weight
Birth- 3kg
6 wks- 3.4 kg
2mo-3.4kg
62
Case Study: Meseret (10)—Pertinent
Physical Exam
 On examination, the thrush is still visible and
lymph nodes are somewhat larger
 Infant diagnostic tests are not yet back. You ask
the nurse to call the lab and they have no record
of the sample
 What would you do now?
63
Case Study: Meseret (11)
 You decide that the child does not require hospitalization
but ask mom to return in two days
 You order:
 CXR
 CD4 count
 Repeat virologic testing
 Test Results:
 The CD4 is 1200, 13%
 DNA PCR results are not ready
 CXR is normal
 Does this child have HIV infection?
64
Case Study: Meseret (12)
 The team decides that the child most likely has
HIV infection and requires treatment
 Thrush
 Failure to thrive ( WHO Stage III)
 Low CD4 (<25% for infant <11months of age)
 What will you tell the mother?
 What will you do to confirm the child’s infection
status?
65
Case Study: Meseret (13)
 Meseret was continued on CTX, nystatin for
thrush and started on ARVs
 Both initial and repeat DNA PCR results were
positive when test results were finally available
66
Case Study: Tsegenet
 Mom brings her 10 week old baby, Tsegenet, for
a return visit
 The baby has been receiving cotrimoxazole
since 4 weeks of age
 She is breastfeeding well and has not been sick
 A DNA PCR test was sent at the previous visit
and mom is anxious to know the results
 The team discussed this family last week during
the multidisciplinary meeting
67
Case Study: Tsegenet (2)
 DNA-PCR results were positive
 The team talked about how to share the news
with the parents
 What will you say to her mother when she
comes to the clinic?
68
Case Study: Tsegenet (3)
 Tsegenet appears well with a normal physical
examination
 Growth is plotted on the 50th percentile for
weight, height and head circumference
 She smiles, makes good eye contact, and
reaches out
 She is EXCLUSIVELY breastfeeding
69
Case Study: Tsegenet (4)—Growth Curve
70
Case Study: Tsegenet (5)—Clinical
Questions
 Given the laboratory result and the clinical
findings, do you think this child is HIV-infected?
 How will you manage the child?
 What will you tell the mother?
71
Case Study: Tsegenet (6)
 Mom returns with the baby in a month
 The repeat DNA PCR test is negative and the
baby is still thriving
 What will you do?
72
Case Study: Tsegenet (7)—Clinical Question
 Which of the following actions would you
consider?





Repeat DNA-PCR testing
CD4
Continue cotrimoxazole
Monitor closely
Rapid antibody screen at 12 months
73
Case Study: Tsegenet (8)—Case Conclusion
 The team was unsure about the lab tests, but
decided to:
 Continue the CTX for now
 Schedule more frequent follow-up, at the same time
as mom’s visits
 Work with the mom to continue exclusive
breastfeeding till she is 6 months then introduce
complementary feeds with continued breastfeeding
 Tsegenet is weaned at 10 months
 At 12 months Tsegenet tested HIV Ab negative
74
Key Points
 Infant diagnosis can be a complex and lengthy process
 Early virologic testing should be used to identify the
infected infant at highest risk for disease progression
 Specialized virologic tests are used to diagnose HIV
infection in a child <18 months
 Two positive virologic tests confirm HIV infection in an exposed
infant
 The presence of HIV antibody in a child >18 months
defines HIV infection
75
Key Points (2)
 Clinical reasoning is critical to diagnosing infants with
HIV
 Virologic tests may be unreliable or unavailable, making
clinical evaluation important
 HIV can be diagnosed without a definitive virologic test in
an ill child with clinical and immunological evidence of
infection
 The diagnosis should be confirmed with virologic testing,
response to treatment and/or antibody testing >18
months
 The multidisciplinary team has numerous critical roles in
this process
 The parent or caretaker is the key player, and must be
educated and supported on this logistically, emotionally,
socially and medically complicated path
76