1. STAGING OF HIV INFECTION, COMMON AND OPPORTUNISTIC INFECTIONS

2. 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?

3. 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).

4. How do we stage? Clinical staging: Immunological staging
WHO staging-commonly used
Immunological staging
CD4 count

5. How many clinical stages are in the WHO clinical staging criteria?
Classification
WHO clinical stage
Asymptomatic 1
Mild 2
Advanced 3
Severe 4

6. 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

7. CD4% does NOT change with age.
CD4 Pattern in Young Children
CD4 counts are high in healthy young children.
Decline to adult levels by 6 yrs.
CD4% does NOT change with age.

8. WHO Immunological Staging
Classification of HIV associated immune deficiency
Age-related CD4 values
≤11 months (%)
12-35 months (%)
36-59 months (%)
≥5 yrs (cells/mm3)
Not Significant
>35
>30
>25
>500
Mild
30-35
25-30
20 -25
Advanced
20-25
15-20
Severe
<25
<20
<15
<200 or <15%

9. WHO Clinical Staging Stage 1 Asymptomatic
Persistent generalised lymphadenopathy (PGL)

10. No HIV related symptoms reported and no signs on examination.
WHO STAGE 1
Asymptomatic
Clinical diagnosis
No HIV related symptoms reported and no signs on examination.

11. Persistent generalized lymphadenopathy (PGL)
WHO STAGE 1
Persistent generalized lymphadenopathy (PGL)
Clinical signs and symptoms
Swollen or enlarged lymph nodes >1 cm at two or more non-contiguous sites, without known cause

12. 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

13. WHO clinical stage 3
Moderate Unexplained malnutrition not adequately responding to standard therapy
Unexplained persistent diarrhea (14 days or more)
Unexplained persistent fever (>37.5OC, intermittent or constant >1 mo)
Persistent oral candidiasis (after 6 weeks of life)
Oral hairy leukoplakia
Acute necrotizing ulcerative gingivitis/periodontis
Lymph node TB
Pulmonary tuberculosis
Severe recurrent bacterial pneumonia
Symptomatic Lymphoid interstitial pneumonitis (LIP)
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.

14. Unexplained persistent Fever
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

15. In older children, productive cough and haemoptysis as well.
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.

16. WHO clinical stage 4
Unexplained severe wasting, or severe malnutrition not adequately responding to standard therapy
Pneumocystis pneumonia (PCP).
Recurrent severe presumed bacterial infection e.g. empyema, pyomyositis, bone/joint infections, meningitis, but excluding pneumonia
Chronic herpes simplex infection
Extrapulmonary tuberculosis
Kaposi’s Sarcoma
Esophageal candidiasis (Candida of trachea, bronchi or lungs)
CNS toxoplasmosis
HIV encephalopathy
CMV infection, retinitis or infection affecting other organs
Extrapulmonary cryptococcosis, including meningitis

17. WHO clinical stage 4
Disseminated endemic mycosis (extra pulmonary histoplasmosis, coccidiomycosis, pennicilliosis
Chronic cryptosporidiosis
Chronic Isosporiasis
Disseminated non-tuberculous mycobacteria infection
Cerebral or B-cell non-non-Hodgkin's lymphoma
Progressive multifocal leukoencephalopathy
HIV associated cardiomyopathy and nephropathy

18. Recurrent severe bacterial infection
WHO clinical Stage 4
Recurrent severe bacterial infection
Types of recurrent severe
bacterial infections
Empyema
Pyomyositis
Bone or Joint infection
Meningitis
Excluding Pneumonia
Signs and Symptoms
Fever accompanied by specific symptoms or signs that localize
infection.
Current episode plus one or more in previous six months
Treatment
Antibiotic treatment
When there pus- Do I&D

19. Photo courtesy of Dr Israel Kalyesubula
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

20. Pneumocystis Pneumonia
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%)

21. Management Supportive IV Cotrimoxazole Oxygen/ventilatory support
WHO clinical Stage 4
Management
Supportive
Oxygen/ventilatory support
Maintain and monitor hydration
Nutritional support
Continue therapy for bacterial pneumonia
IV Cotrimoxazole
Trimethoprim (TMP): mg/kg/day
6-8 hourly
Sulphamethoxazole (SMX): mg
Oral Cotrimoxazole
TMP: 20 mg/kg/day 6-8 hourly
SMX: 100mg OR
IV Pentamidine 4mg/kg/day OD
Dapsone 2mg/kg/OD
Course: 2-3 weeks
Add prednisone 2 mg/kg for 7-14 days in severely ill children 21 21

22. 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 22 22

23. Esophageal Candidiasis
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 23 23

24. Cryptococcal Meningitis
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. 24 24

25. Cryptococcal Meningitis
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 25 25

26. Toxoplasmosis Hepatosplenomegaly Fever Chorioretinitis Seizures
WHO clinical Stage 4
Toxoplasmosis
Congenital Toxoplasmosis
Hepatosplenomegaly
Fever
Chorioretinitis
Seizures
Periventricular calcifications
Hypodense lesions with ring enhancement
Presents in 2 forms
Congenital Toxoplasmosis- Diffuse disease
Acquired CNS Toxoplasmosis 26 26

27. CNS Toxoplasmosis Diagnosis Toxoplasma antibodies (IgM)
WHO clinical Stage 4
CNS Toxoplasmosis
Diagnosis
Toxoplasma antibodies (IgM)
CNS Imaging (Ring enhancing lesions on MRI)
Response to empiric treatment most practical means of making a diagnosis
Fever
Headache,
Focal neurological signs
Convulsions. 27 27

28. Toxoplasmosis WHO clinical Stage 4
Cranial CT showing ring-enhancing lesion in the brain 28 28

29. Toxoplasmosis - Treatment
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
Sulphadiazine mg/kg/dose QID for 6 weeks
Plus
Folinic acid 5-20 mg 3 times weekly
Alternative regimens
Cotrimoxazole (15-20mg/kg Trimethoprim plus 100mg Sulfamethoxazole) IV or Oral BD
Clindamycin (5 – 7mg/kg QID orally) plus Pyrimethamine and Folinic acid
Prophylaxis –Cotrimoxazole prophylaxis

30. Cryptosporidiosis and Isosporiasis
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

31. Case Study Practice: Staging & Managing OIs

32. Recurrent Broncho Pneumonia
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?
Qn 2: What WHO clinical stage is this?
Qn 3: How would you treat this child?
Recurrent Broncho Pneumonia
Stage 3
Admit, Parenteral Antibiotics, Start ARV’s as soon as possible.

33. Pneumocystis Jiroveci Pneumonia
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?
Question 2: What is the WHO clinical stage?
Question 3: What is the treatment of this condition?
Pneumocystis Jiroveci Pneumonia
Stage 4
Admit, Oxygen, IV Septrin, Steroids, ARV’s as soon as possible

34. Case 3 Question 1: What is the diagnosis and WHO clinical stage?
Question 2: What is the treatment of this condition?
Herpes simplex, Stage 2
Acyclovir cream, analgesia, add antibiotics if there is bacterial infection
Photograph courtesy of Dr Israel Kalyesubula

35. Case 4: Question 1: What is the diagnosis? Question 2: Kaposi sarcoma
How would you confirm the diagnosis?
Question 3: What clinical stage is this child in?
Kaposi sarcoma
Biopsy
Stage 4
Photograph courtesy of Dr Israel Kalyesubula

36. Nystatin, Ketoconazole
Case 5
Question 1: What is the diagnosis?
Question 2: In what clinical stage is this child?
Question 3: What is the treatment of this condition?
Oral Candidiasis
Stage 3
Nystatin, Ketoconazole
Photograph courtesy of Dr Israel Kalyesubula

37. Serum Toxo titers, Brain CT scan
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?
Question 2: How would you investigate this patient?
Question 3: What is the clinical stage?
Toxoplasmosis
Serum Toxo titers, Brain CT scan
Stage 4

38. 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?
Question 2: How would you diagnose this condition?
Question 3: How would you treat this condition?
Cryptococcal meningitis, Stage 4
Serum Crag, Lumbar Puncture, CSF Indian stain
Admit, IV Amphotericin B, ARVs as soon as possible

39. 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?
Question 2: What possible agents could cause this diarrhea?
Modified ZN on stool, HIV serology
Cryptosporidium parvum, isospora belli

40. Lymphoid Interstitial Pneumonitis (LIP)
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?
Qn2: what is the WHO clinical stage?
Question 2: How would you manage this patient?
Lymphoid Interstitial Pneumonitis (LIP)
Stage 3
Antibiotics, ARVs

41. 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

42. 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?
How would you treat this child?
Stage 4
Ketocanazole, ARVs

43. Case 12 Question 1: What is the diagnosis? Question 2:
What is WHO clinical Stage?
Question 3:
What is the treatment of this condition?
Herpes Zoster
Stage 2
Photograph courtesy of Dr Israel Kalyesubula
Acyclovir

44. Acknowledge Dr Israel Kalyesubula for all the photographs.