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?

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: Immunological staging WHO staging-commonly used Immunological staging 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% 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.

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 -25 350-499 Advanced 20-25 15-20 200 - 349 Severe <25 <20 <15 <200 or <15%

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

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.

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

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

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.

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

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.

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

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

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

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

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%)

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): 15- 20mg/kg/day 6-8 hourly Sulphamethoxazole (SMX): 75- 100mg 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

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

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

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

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

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

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

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

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 25 - 50 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

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

Case Study Practice: Staging & Managing OIs

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.

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

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

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

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

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

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

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

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

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

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

Acknowledge Dr Israel Kalyesubula for all the photographs.