STAGING OF HIV INFECTION,
COMMON AND OPPORTUNISTIC
INFECTIONS
Key Questions
•Why do we need to do Staging of HIV in infected
children?
•What are the different methods of staging?
•What are the common opportunistic infections in
HIV infected children and how do you treat them?
•What tool can I use to easily identify , stage and
treat OI’s in HIV infected children?
2
Why do we do Staging?
• Provides a guide to the timing of initiation of
ART
• Provides a guide to prognosis and
interventions needed at the different stages
• Provides guidance in monitoring response to
therapy (treatment failure or improvement).
How do we stage?
• Clinical staging:
o WHO staging-commonly used
 Immunological staging
o CD4 count
How many clinical stages are in the
WHO clinical staging criteria?
Classification
WHO clinical stage
Asymptomatic
1
Mild
2
Advanced
3
Severe
4
Immunological Staging
• Differences in CD4 counts between adults and
children
– Absolute CD4 count varies with age
–
Absolute CD4 count is higher in healthy
children than in adults.
 Cut-off CD4 counts CHANGE with age
in children < 5 years; CD4 percentage more
constant
CD4 Pattern in Young
Children
6000
4000
5th percentile
95th percentile
2000
0
0 4 9 12
24
•CD4 counts are high in
healthy young children.
•Decline to adult levels by 6
yrs.
60
Age in Months
Age-related Decrease in CD4+
Percentage
80
•CD4% does NOT
change with age.
CD4+ %
CD+ Number/mm3
Age-related Decrease in CD4+ Number
60
5th percentile
95th percentile
40
20
0
0
4 9 12
24
60
Age in Months
7
WHO Immunological Staging
Classification of
Age-related CD4 values
HIV associated
immune
≤11
12-35
36-59
≥5 yrs
deficiency
months (%) months (%) months (%) (cells/mm3)
Not Significant
>35
>30
>25
>500
Mild
30-35
25-30
20 -25
350-499
Advanced
25-30
20-25
15-20
200 - 349
Severe
<25
<20
<15
<200 or
<15%
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WHO Clinical Staging
Stage 1
• Asymptomatic
• Persistent generalised lymphadenopathy
(PGL)
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WHO STAGE 1
Asymptomatic
Clinical diagnosis
No HIV related symptoms reported and no signs on
examination.
WHO STAGE 1
Persistent generalized lymphadenopathy (PGL)
Clinical signs and
symptoms
•Swollen or enlarged
lymph nodes >1 cm at
two or more noncontiguous sites, without
known cause
WHO clinical stage 2
• Unexplained persistent
hepatosplenomegaly
• Papular pruritic eruptions
• Fungal nail infections
• Angular cheilitis
• Lineal gingival erythema
• Extensive wart virus
infections
• Extensive molluscum
contagiosum infection
• Recurrent oral ulcerations
• Unexplained bilateral
parotid enlargement
• Herpes zoster
• Recurrent or chronic
upper respiratory
infection (URI): otitis
media, otorrhea, sinusitis,
tonsillitis
12
WHO clinical stage 3
• Moderate Unexplained
malnutrition not adequately
responding to standard therapy
• Lymph node TB
• Unexplained persistent diarrhea
(14 days or more)
• Severe recurrent bacterial
pneumonia
• Unexplained persistent fever
(>37.5OC, intermittent or
constant >1 mo)
• Symptomatic Lymphoid
interstitial pneumonitis (LIP)
• Persistent oral candidiasis (after 6
weeks of life)
• Oral hairy leukoplakia
• Pulmonary tuberculosis
• Chronic HIV-associated lung
disease including bronchiectasis
• Unexplained anemia (<8 gm/dL),
neutropenia (<1,000/mm3 ), or
chronic thrombocytopenia
(<50,000/mm3) for >1 month.
• Acute necrotizing ulcerative
gingivitis/periodontis
13
WHO clinical Stage 3
Unexplained Persistent Diarrhea:
Unexplained persistent (14 days or more) diarrhea(loose or
watery stool, three or more times daily) not responding to
standard treatment
Unexplained persistent Fever
•Reports of fever or night sweats for longer than one month.
•Intermittent or constant
•Reported lack of response to antibiotics or antimalarials.
•No other obvious foci of disease reported or found on
examination.
•Malaria must be excluded
WHO clinical Stage 3
Severe recurrent bacterial pneumonia
Cough with fast breathing, chest in drawing, nasal flaring,
wheezing and grunting.
Crackles or consolidation on auscultation.
Responds to course of antibiotics.
Current episode plus one or more in previous six months.
Pulmonary TB
•Non-specific symptoms, e.g. chronic cough, fever, night sweats,
anorexia and weight loss.
•In older children, productive cough and haemoptysis as
well.
•Abnormal CXR.
WHO clinical stage 4
• Unexplained severe wasting,
or severe malnutrition not
adequately responding to
standard therapy
• Extrapulmonary tuberculosis
• Pneumocystis pneumonia
(PCP).
• Esophageal candidiasis
(Candida of trachea, bronchi
or lungs)
• Recurrent severe presumed
bacterial infection e.g.
empyema, pyomyositis,
bone/joint infections,
meningitis, but excluding
pneumonia
• CNS toxoplasmosis
• Chronic herpes simplex
infection
• Kaposi’s Sarcoma
• HIV encephalopathy
• CMV infection, retinitis or
infection affecting other
organs
• Extrapulmonary
cryptococcosis, including
meningitis
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WHO clinical stage 4
• Disseminated endemic
mycosis (extra pulmonary
histoplasmosis,
coccidiomycosis,
pennicilliosis
• Cerebral or B-cell nonnon-Hodgkin's lymphoma
• Chronic cryptosporidiosis
• HIV associated
cardiomyopathy and
nephropathy
• Chronic Isosporiasis
• Progressive multifocal
leukoencephalopathy
• Disseminated nontuberculous mycobacteria
infection
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WHO clinical Stage 4
Recurrent severe bacterial infection
Types of recurrent severe
bacterial infections
• Empyema
• Pyomyositis
• Bone or Joint infection
• Meningitis
• Excluding Pneumonia
Treatment
•Antibiotic treatment
•When there pus- Do I&D
Signs and Symptoms
• Fever accompanied by
specific symptoms or signs
that localize
infection.
• Current episode plus one or
more in previous six months
NN is a one year old girl with multiple
swellings one week prior to coming to
hospital.
The one on the buttock burst on the
third admission day spontaneously and
drained green offensive pus.
Green debrie can be seen in both
incised abscesses.
Photo courtesy of Dr Israel Kalyesubula
WHO clinical Stage 4
Pneumocystis Pneumonia
• Caused by Pneumocystis
Jiroveci (fungus)
• Major cause of mortality
and morbidity in HIV
infected children
Clinical presentation:
• Usually less than 1 year
• Cough
• Fast breathing
• Difficulty in breathing
• Low grade fever or
afebrile
• Hypoxemia (paO2 <
90%)
WHO clinical Stage 4
Management
• Supportive
– Oxygen/ventilatory
support
– Maintain and monitor
hydration
– Nutritional support
– Continue therapy for
bacterial pneumonia
IV Cotrimoxazole
Trimethoprim (TMP): 15- 20mg/kg/day
6-8 hourly
Sulphamethoxazole (SMX): 75- 100mg
Oral Cotrimoxazole
TMP: 20 mg/kg/day 6-8 hourly
SMX: 100mg
OR
1.
IV Pentamidine 4mg/kg/day OD
2. Dapsone 2mg/kg/OD
Course: 2-3 weeks
Add prednisone 2 mg/kg for 7-14
days in severely ill children
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PCP Prophylaxis
Who Should Receive Prophylaxis?
All HIV exposed and HIV infected infants should
receive cotrimoxazole prophylaxis from 6 weeks of
age
Dose: 10 mg/kg daily or Dapsone 2mg/kg daily
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WHO clinical Stage 4
Esophageal Candidiasis
• Causes painful swallowing
• Results in inadequate oral intake with
consequences of:
– Dehydration, malnutrition and
death
Treatment:
– Local treatments (Nystatin, GV)
– Fluconazole 3-6 mg/kg/OD for 2-3
wks.
– Ketoconazole 5-10mg/kg/in 1or 2
divided dose
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WHO clinical Stage 4
Cryptococcal Meningitis
• Less common in
children than adults
• usually sub acute, fever
with increasing severe
headache.
• meningism, confusion,
behavioral changes.
• Seizures
Diagnosis
• Do LP and Indian ink
stain of CSF
• Cryptococcal antigen
test on CSF.
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WHO clinical Stage 4
Cryptococcal Meningitis
Treatment
Initial treatment
• Amphotericin B 0.7-1mg/kg for 14 days then
Fluconazole 3-6mg/kg OD X 8 weeks
• May need to do therapeutic LP’s to relieve headache
Maintenance treatment (secondary prophylaxis)
• Fluconazole 3 mg/kg OD for life
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WHO clinical Stage 4
Toxoplasmosis
Presents in 2 forms
• Congenital ToxoplasmosisDiffuse disease
• Acquired CNS
Toxoplasmosis
Congenital Toxoplasmosis
•
•
•
•
•
Hepatosplenomegaly
Fever
Chorioretinitis
Seizures
Periventricular
calcifications
• Hypodense lesions with
ring enhancement
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WHO clinical Stage 4
CNS Toxoplasmosis
• Fever
• Headache,
• Focal neurological signs
• Convulsions.
Diagnosis
• Toxoplasma antibodies
(IgM)
• CNS Imaging (Ring
enhancing lesions on MRI)
• Response to empiric
treatment most practical
means of making a
diagnosis
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WHO clinical Stage 4
Toxoplasmosis
Cranial CT showing ring-enhancing lesion
in the brain
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WHO clinical Stage 4
CNS
Toxoplasmosis-Treatment
Toxoplasmosis
- Treatment
Preferred regimen
• Pyrimethamine 2mg/Kg/day
for 3 days maximum 25mg,
then 1mg/kg/day for
6weeks
Alternative regimens
• Cotrimoxazole (15-20mg/kg
Trimethoprim plus 100mg
Sulfamethoxazole) IV or
Oral BD
• Sulphadiazine 25 - 50
mg/kg/dose QID for 6
weeks
Plus
– Folinic acid 5-20 mg 3
times weekly
• Clindamycin (5 – 7mg/kg
QID orally) plus
Pyrimethamine and Folinic
acid
Prophylaxis –Cotrimoxazole prophylaxis
WHO clinical Stage 4
Cryptosporidiosis and Isosporiasis
• Usually present with chronic diarrhoea in
advanced HIV infection
• Diagnosis is by stool analysis: modified ZN
staining, PCR
• Treatment: Paromomycin, Cotrimoxazole
• Prevention: Cotrimoxazole
Case Study Practice:
Staging & Managing OIs
31
Case 1
A 3 year old HIV infected girl presents with a 1 week’s history of
cough. For the last 2 days she has had a high grade fever and
difficulty in breathing. On examination temperature is 38.4
degrees C, the respiratory rate is 60bpm, She looks very sick. The
chest has bilateral coarse crepitations. This is her 2nd episode of
this illness in 6 months
Qn 1: What is the possible diagnosis in this child?
Recurrent Broncho Pneumonia
Qn 2: What WHO clinical stage is this?
Stage 3
Qn 3: How would you treat this child?
•Admit, Parenteral Antibiotics, Start ARV’s as soon as possible.
32
Case 2
Opio, a 9 month old baby with sudden onset of cough and
difficulty in breathing. On examination, temperature 37.5
degrees C,Respiratory rate 90 bpm, chest in-drawing and
the chest is clear on auscultation.
• Question 1: What is the most likely diagnosis?
Pneumocystis Jiroveci Pneumonia
• Question 2: What is the WHO clinical stage?
Stage 4
• Question 3: What is the treatment of this condition?
Admit, Oxygen, IV Septrin, Steroids, ARV’s as soon as possible
33
Case 3
Question 1: What is
the diagnosis and
WHO clinical stage?
Herpes simplex,
Stage 2
Question 2: What is
the treatment of this
condition?
Acyclovir cream, analgesia,
add antibiotics if there is
bacterial infection
Photograph courtesy of Dr Israel Kalyesubula
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Case 4:
Question 1:
What is the diagnosis?
Kaposi sarcoma
Question 2:
How would you confirm the
diagnosis?
Biopsy
Question 3: What clinical
stage is this child in?
Stage 4
Photograph courtesy of Dr Israel Kalyesubula
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Case 5
Question 1: What is the
diagnosis?
Oral Candidiasis
Question 2: In what clinical
stage is this child?
Stage 3
Question 3: What is the
treatment of this condition?
Nystatin,
Ketoconazole
Photograph courtesy of Dr Israel Kalyesubula
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Case 6
Racheal, an HIV infected 16 year old girl presents with
seizures and weakness of the right side of the body. Her
CD4 count is 86 cells/uL.
• Question 1: What would you suspect in this patient?
Toxoplasmosis
• Question 2: How would you investigate this patient?
Serum Toxo titers,
Brain CT scan
• Question 3: What is the clinical stage?
Stage 4
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Case 7
• Namubiru, an 11 year old HIV infected girl who has
never had any symptoms has CD4 count 60cells/uL.
She presents today with 2 days history of severe
headache and photophobia.
• Question 1: What is the likely diagnosis and WHO
stage?
Cryptococcal meningitis,
Stage 4
• Question 2: How would you diagnose this condition?
Serum Crag, Lumbar Puncture, CSF
Indian stain
• Question 3: How would you treat this condition?
Admit, IV Amphotericin B, ARVs as soon as possible
Case 8
Okello, a 15 year old boy presents with a
3 week history of profuse diarrhea.
• Question 1: How would you investigate
this patient?
Modified ZN on stool, HIV serology
• Question 2: What possible agents could
cause this diarrhea?
Cryptosporidium parvum, isospora belli
Case 9
Waiswa, a 9 year old boy presents with a 2 year
history of on and off cough. He has received 2 full
courses of TB drugs. On examination he is in fair
general condition, has bilateral parotid enlargement,
digital clubbing and hepatosplenomegaly.
– Question 1: What is the likely diagnosis?
Lymphoid Interstitial Pneumonitis (LIP)
– Qn2: what is the WHO clinical stage?
Stage 3
– Question 2: How would you manage this patient?
Antibiotics, ARVs
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Case 10
• Amoding, a 6 year old HIV infected girl
presents to the clinic with severe malnutrition
non responding to standard therapy and
persistent diarrhea.
• Question 3: In what clinical stage would you
place this child? Why?
Stage 4
Case 11
• A 3year old boy is HIV positive and he is
unable to walk on his own, can only say
“mama” in his vocabulary. In addition he is
suffering from oral thrush and recurrent
fevers. In what WHO clinical stage is he
• What is the clinical stage?
Stage 4
• How would you treat this child?
Ketocanazole, ARVs
Case 12
Question 1:
What is the diagnosis?
Herpes Zoster
Question 2:
What is WHO clinical
Stage?
Stage 2
Question 3:
What is the treatment of
this condition?
Photograph courtesy of Dr Israel Kalyesubula
Acyclovir
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Acknowledge Dr Israel Kalyesubula for all the
photographs.