Additional File B. Severity Grading Guidelines

Additional File B. Severity grading guidelines

Table 1. Guidelines for Grading Patient Symptoms† Grade 1 Grade 2 Grade 3 Grade 4 MILD MODERATE SEVERE LIFE THREATENING Subjective N/A Present (Yes) N/A N/A fever in the past 24 h Weakness Mild decrease in activity, Moderate decrease in Not participating in Lethargic still playing activity, playing limited usual activities, not playing Muscle and/or Mild localised Mild diffuse complaints Objective weakness; N/A joint aches* complaints function limited Headache* Mild, no therapy Transient, moderate; Severe; responds to Intractable; requires required therapy required initial narcotic therapy repeated narcotic therapy Anorexia Decreased appetite, but Decreased appetite, Refusing to breast feed, Refusing to breast feed, still taking solid food avoiding solid food appetite very decreased, appetite very decreased, no solids or liquids taken no solids or liquids (< 2 years < 12 hr; > 2 taken (< 2 years < 12 hr; years < 24 hr) > 2 years < 24 hr) Nausea* Mild discomfort; Moderate discomfort; Severe discomfort; no Minimal fluid intake maintains reasonable intake decreased significant intake; intake significantly; some activities limited activity limited Vomiting Transient emesis Occasional or moderate Orthostatic hypotension Hypotensive shock or vomiting or IV fluids required hospitalization required for IV fluid therapy Abdominal Mild Moderate – no treatment Moderate to severe – Severe – hospitalized for pain* needed treatment needed treatment Diarrhea Transient 3-4 loose 5-7 loose stools/day Orthostatic hypotension Hypotensive shock or stools/day or > 7 loose stools/day or hospitalization for IV IV fluids required fluid therapy required Cough Transient – no treatment Continuous, requires Uncontrolled Cyanosis, stridor, severe required treatment shortness of breath Pruritus Pruritus without rash Pruritic rash, pruritus Mild urticaria Severe urticaria, without rash that disturbs anaphylaxis, angioedema sleep Tinnitus* Mild ringing or roaring Moderate ringing or Severe ringing or roaring N/A sound roaring sound sound with associated hearing loss Behavioural Mild difficulty Moderate confusion or Severe confusion or Toxic psychosis; changes concentrating; mild agitation; some agitation; Needs hospitalization required confusion or agitation; limitation of activities of assistance for activities activities of daily living daily living; minimal of daily living; therapy unaffected; no treatment treatment required “Flu” Mild nasal congestion, Moderate nasal N/A (if severe, classify N/A (if life-threatening, (viral URI) mild rhinorrhea, no congestion, moderate individual symptoms) classify individual cough rhinorrhea, cough symptoms) present

Convulsion N/A N/A Localized or generalized Status epilepticus seizure * Assess only in children > 3 years of age. Answer N/A for younger children and those unable to answer. † Reference – Based on WHO Toxicity Grading Scale for Determining the Severity of Adverse Events

1 February 2008 Table 2. Grading Physical Examination Findings Grade 1 Grade 2 Grade 3 Grade 4 MILD MODERATE SEVERE LIFE-THREATENING Temperature* 38.0-38.4C 38.5-40.0C > 40.0C Sustained fever, equal or (tympanic greater than 40.0C for membrane) longer than 5 days Dehydration Normal skin turgor and Skin dry with + tenting, dry Skin clammy with lack of turgor, parched / cracked mucous ** touch, moist mucous mucous membranes, eyes membranes, sunken eyes, no tears, sunken fontanelle, CNS – membranes, tears present, deep set, decreased tears, lethargic, pusle increased, no urine output eyes normal, fontanelle flat, fontanelle soft, CNS – CNS – consolable, pulse irritable, pulse slightly regular, urine output normal increased, urine output decreased Jaundice Slight yellowing of sclera Moderate yellowing of sclera Severe yellowing of sclera N/A and conjunctiva and conjunctiva, yellowing and conjunctiva, yellowing of mucous membranes of skin Pallor Minimally pale conjunctiva, Moderately pale conjunctiva, Paper white conjunctiva, nail N/A nail beds nail beds beds, palms. Eyes Redness, conjunctival Eye pain, periorbital edema, Blindness or visual field N/A injection, conjunctival exophthalmos, blurred defecits, signs of discharge, excessive tearing vision, miosis, mydriasis, endophthalnitis, paralysis of double-vision, extraocular muscles, papilledema Ears Edema or hyperemia of pina, Discharge from canal, Perforated ear drum N/A tenderness or pina, red- swollen ear drum Oropharynx Hyperemia, pigmentation, Pharyngeal exudates or Tonsilar swelling, gum Tonsilar obstruction erythema bleeding, blisters, ulceration Facial edema Present, mild swelling of Moderate swelling of eyes, Severe swelling involving Airway compromise eyes face eyes, face, and mucous membranes; unable to open eyes Neck Non-tender Tender lymphadenopathy, Tracheal deviation Stridor lymphadenopathy, erythema swelling, tenderness, glandular enlargement Chest Mildly increased RR (for Moderately increased RR, Rapid RR (< 2 months > 60, Cyanosis age, temperature), transient diffuse or persistent 2-12 months > 50, 1-5 years or localised adventitious adventitious sounds > 40, adults > 30)* nasal sounds flaring, retractions Cardio-vascular Grade 1 murmur Asymptomatic change in Recurrent/persistent change Change in rhythm or extra System (CVS) rhythm or extra heart sounds in rhythm or extra heart heart sounds that require (no treatment required); sounds (treatment required), treatment and/or Grade 2 murmur Grade 3-4 murmur hospitalization; Grade 5-6 murmur Abdomen Normal bowel sounds, mild Normal or mildly abnormal Severely abnormal bowel Absent bowel sounds. localised tenderness, and/or bowel sounds, moderate or sounds, severe tenderness to Involuntary rigidity liver palpable 2-4 cm below diffuse tenderness; and/or palpation. Evidence of the right costal margin mild to moderately enlarged peritoneal irritation and/or (RCM), and/or spleen liver (4-6 cm below the significant enlargement of palpable, and/or umbilical RCM) and/or spleen palpable liver (> 6 cm below the hernia present up to half-way between RCM) and/or spleen palpable umbilicus and symphysis beyond half-way between pubis umbilicus and symphysis pubis Skin† Localised rash, erythema, or Diffuse, maculopapular rash, Vesiculation, moist Exfoliative dermatitis, pruritis dry desquamation desquamation, or ulceration mucous membrane involvement or erythema multiforme or suspected Stevens-Johnson or necrosis requiring surgery * Reference - DMID Pediatric Toxicity Tables, May 2001, Drug Fever (Rectal) ** Reference – The Harriet Lane Handbook, 15th edition, 2000 † Reference – WHO Toxicity Grading Scale for Determining the Severity of Adverse Events

1 February 2008 Table 3. Grading Neurologic Examination Findings Grade 1 Grade 2 Grade 3 Grade 4 MILD MODERATE SEVERE LIFE-THREATENING Hearing < 4 years: N/A < 4 years: N/A < 4 years: Any evidence N/A > 4 years: Decreased > 4 years: Decreased of hearing impairment hearing in one ear hearing in both ears or > 4 years: Severe severe impairment in one impairment in both ears ear Nystagmus 3 or fewer beats of lateral More than 3 beats of Sustained lateral N/A nystagmus lateral nystagmus nystagmus, any vertical or rotary nystagmus Tablet test Difficulty grasping tablet Unable to pick up tablet Unable to grasp tablet N/A but able to pick up without dropping Heel-toe 2-4 years: Able to take at 2-4 years: Unable to take 2-4 years: Unable to walk N/A least 5 steps 5 steps > 4 years: Unable to > 4 years: Able to take at > 4 years: Unable to take perform tandem walk least 5 tandem steps 5 tandem steps

Romberg > 4 years: Unable to stand > 4 years: Unable to stand > 4 years: Unable to stand N/A for 30 seconds with eyes for 15 seconds with eyes with feet together with closed closed eyes open or closed Clinical No therapy; monitor May require minimal Requires medical care Requires active medical symptoms / condition intervention and and possible intervention, sign (not monitoring hospitalization hospitalization, or hospice otherwise care specified)

1 February 2008 Table 4. Guidelines for Grading of Laboratory Abnormalities Grade 1 Grade 2 Grade 3 Grade 4 MILD MODERATE SEVERE LIFE- THREATENING Absolute neutrophil 750-1200 400-749 250-399 < 250 count* (/mm3) Hemoglobin (g/dL) 9.0 – 9.9 7.0 – 8.9 5.0 – 6.9 < 5.0

Platelets (/mm3)* N/A 50,000-75,000 25,000-49,999 < 25,000

ALT (U/L)** 1.1-4.9 x ULN 5.0-9.9 x ULN 10.0-15.0 x ULN > 15.0 x ULN (50 – 224) (225 – 449) (450 – 675) (> 675)

Bilirubin (U/L)* 1.1-1.9 x ULN 2.0-2.9 x ULN 3.0-7.5 x ULN > 7.5 x ULN

Creatinine (mg/dl))* 0.6-0.8 0.9-1.1 1.2-1.5 > 1.5 Age < 2 years Creatinine (mg/dl))* 0.7-1.0 1.1-1.6 1.7-2.0 > 2.0 Age > 2 years Laboratory values Abnormal but requiring Sufficiently abnormal to Sufficiently severe to Life-threatening (not otherwise no immediate require evaluation as to require evaluation and severity; requires specified) intervention; follow causality and perhaps treatment immediate evaluation, mild therapeutic treatment, and usually intervention hospitalization *Reference – DMID Pediatric Toxicity Tables, May 2001 ** Reference – DAIDS Pediatric guidelines

1 February 2008