Malaria sévère

SEVERE MALARIA FOR ANESTHESIOLOGISTS JournĂŠe Chirurgie-Anesthesie MSF 2014

Estrella Lasry Tropical Medicine Advisor, MSF-F

MALARIA GENERAL FACTS - Nearly

half of the population in the world is at risk of becoming infected with malaria, specially in low income countries (over 108 endemic). 1

- WHO estimates around 200 million cases (85% in WHO African Region) and in 2012 around 600.000 deaths were due to malaria (91% in Africa, 86% in in children under 5 yrs ). 2 - In 2012, MSF treated >1,642,800 confirmed malaria cases in more than 20 countries 1 Fact sheet Malaria WHO 2 Source World Malaria Report WHO 2012

Severe Malaria for

THE REAL WORLD MALARIA MAP

MALI; 0%

MAURITANIA; 3% NIGER; 2% NIGERIA; 0%

BURKINA FASO; 2%

MADAGASCAR; 10%

300,861 CASES OF MALARIA TREATED

BY MSFF IN 2013, 1.6 MILLION BY ALL MSF SECTIONS

IVORY COAST; 19%

HAITI; 3%

CAR; 29%

CHAD; 12%

ETHIOPIA; 1%

CONGO BRAZZA; 1% DRC; 19%

MALARIA LIFE CYCLE

DIAGNOSIS Microscopy: -Think film (Goutte epaisse): identify infection -Thin film (Frottis mince): identify species and parasitaemia -Fluorescent microscopy Rapid Diagnostic Tests: antigen detection tests -HRP2: Sensitivity 98%, Specificity 100%, long negativization -pLDH: Sensitivity 97.5%, Specificity 100%, short negativization

PCR: currently the gold standard, but also not feasible in our context

SEQUESTRATION

Severe Malaria for

SEVERE MALARIA Definition: Confirmation of Plasmodium (generally P. falciparum) infection with clinical or laboratory evidence of vital organ dysfunction (WHO)

Clinical Features -Impaired consciousness (incl. coma) -Prostration -Multiple convulsions (>2 in 24h) -Deep breathing and/or Respiratory distress -Acute pulmonary edema and acute respiratory distress syndrome -Circulatory collapse or shock (Systolic BP adults <70 mmHg, children <50 mmHg) -Acute kidney injury (haemoglobinuria) -Clinical jaundice+evidence of other organ dysfunction -Abnormal bleeding

Laboratory Findings -Hypoglycaemia (<2.2 mmol/L or 40mg/dL) -Metabolic acidosis (plasma bicarbonate <15 mmol/L) -Severe normocytic anaemia (Hb<5g/dL or Htc<15%) -Haemoglobinuria -Hyperlactatemia (lactate >5mmol/L) -Renal impairment (Serum Creat>265 umol/L) -Pulmonary oedema (on X-ray) -Hyperparasitaemia (> 2% of RBC or 100,000/Îźl in low transmission areas or > 5% of RBC or 250 000/Îźl in areas of high stable malaria transmission intensity)

TRANSMISSION & SEVERITY High transmission settings (hyperendemic): -Higher risk of Severe Malarial Anaemia (SMA) 1-3 years -Higher risk of Cerebral Malaria (CM) 2-6 years All settings -Children: seizures, SMA -Adults: hyperparasitaemia, acute renal failure -All: CM, shock, respiratory arrest, acidosis

CEREBRAL MALARIA Definition: 1. Confirmed malarial parasitaemia AND 2. BCS <3 (or GCS < 9) AND 3. No other identifiable causes of coma (hypoglycaemia, meningitis, post-ictal state) Histology: cerebral sequestration of parasitized erythrocytes (in autopsy studies this is not seen in 25% of cases diagnosed as CM) Expected mortality: 17.8% (Malawi), 18% (AQUAMAT)

Admission MR images (A and B): T2 and SWI. Diffuse petechial hemorrhages present throughout the brain (particularly the gray-white junction, corpus callosum, and internal capsule) are seen only on the SWI sequence.

Nickerson J et al. AJNR Am J Neuroradiol 2009;30:e85-e86

Š2009 by American Society of Neuroradiology

SPECIFIC CLINICAL EVALUATION CM 1.

2.

3.

4.

Diagnosis: RDT/Microscopy Full physical exam Glycaemia Neurologic exam 1. BCS or GCS: score is inversely related to mortality 2. Fundoscopy 5. Lumbar puncture 1. Mean opening pressure: 16 cm H2O (12 mmHg) 2. None or very few WBC 3. Glucose < 61 mg/dL (3.4 mmol/L) 4. Low protein levels Other 6. Hb: for all cases of Severe Malaria 7. Lactate More 8. Electrolytes 9. FBC

LUMBAR PUNCTURE IN COMA + MALARIA DX Characteristics 1. Mean opening pressure: 16 cm H2O (12 mmHg) 2. None or very few WBC 3. Glucose < 61 mg/dL (3.4 mmol/L) 4. Low protein levels

Lumbar puncture (LP) can be done if ALL THREE of the following apply: 路 Doctor trained to perform the procedure AND 路 Laboratory personnel skilled in cerebrospinal fluid analysis AND 路 The child has NO contra-indications to having an LP Contraindications 1. Child in a coma an not possible to assess papilloedema/intracranial hypertension 2. Coagulation alterations 3. Cardiopulmonary instability 4. Site infection

SEVERE MALARIAL ANAEMIA

SEVERE MALARIAL ANAEMIA

SEVERE MALARIAL ANAEMIA

HYPOGLYCAEMIA

Severe Malaria

Severe Bacterial infection + Malaria

Severely ill child with Positive Malaria slide

Severe Malaria + Bacteraemia

TREATMENT OF SEVERE MALARIA 1. Antimalarials: min 24h of injectable antimalarials

• Artesunate injectable: 2.4 mg/kg • Artemether IM • Quinine/Quinidine • Pre-referral treatment: Artesunate rectal *always relay with 3 days of ACT (Doxy or SP if ttm

with Quinine)

TREATMENT OF SEVERE MALARIA II 2. Paracetamol: 15 mg/kg every 6h (to prevent convulsions in ↑T) 3. Maintenance Fluids: ‘4-2-1’ rule. For CM give 2/3 of this amount First 10kg (0-10kg) give 4ml/kg/hr  40 ml/hr for a 10 kg child Next 10kg (10-20kg) give 2ml/kg/hr additional 20 kg child gets 40ml/hr + 20ml/hr = 60 ml/hr For each kg above 20kg give 1ml/kg/hr extra over 60ml/hr 4. Transfusion if Hb <4 or 4-6+decompensation 5. Other: • Antibiotics • Anticonvulsivants

SUMMARY 1. Most Severe Malaria is due to P. Falciparum 2. Highly Sensitive Diagnosis With Point Of Care Rapid Diagnostic Tests 3. Treatment Of Uncomplicated Malaria With Artemisinin Combination Therapy 4. Treatment Of Severe Malaria With Injectable Artesunate 5. NEED FOR PUBLIC HEALTH INTERVENTIONS INCLUDING VECTOR CONTROL TO CONTROL INCIDENCE

THANK YOU!

MANAGEMENT III LP can be done

LP cannot be done

Case 1

Case 2

Case 3

Case 4

LP confirms Bacterial Meningitis

LP excludes Bacterial Meningitis

Child improves and LP can be done on day 2-3

LP cannot be done

IV Antimalarial min 24h (Artesunate>Artemether>Quinine) IV Ceftriaxone 100 mg/kg x 3 IV Ceftriaxone days + Amoxy Confirmed 100 mg/kg x 10 (or Amoxy-clav) meningitis = days 50 mg/kg/d BD Case 1 up to 7 days (risk of sepsis)

Ceftriaxone 100 Ceftriaxone 100 Excludes mg/kg If NO mg/kg If meningitis = improvement improvement Case 2 after 3 days: after 3 days: Treat as Case 1 Treat as Case 2

MANAGEMENT IV 1. Seizures: up to 70% of children with SM 1. Benzodiazepines 2. Diazepam 0.4 mg/kg IV/IR 3. Lorazepam 0.1 mg/kg IV/IO (not in MSF protocol) 4. *repeat once if maintained seizures after 5 min 5. Phenobarbital: 15-20 mg/kg slow IV 6. Phenytoin: 18 mg/kg in 100 mL NaCl 0.9% IV, 20 min 2. Persistent seizures: 1. Phenobarbital: 5-15 mg/kg/d oral OD or IV (dose/2) 2. Phenytoin: 5 mg/kg BD

NURSING 1. Changing positions 2. NG tube: for patients unable to eat/drink in 24-48h 1. Oral medication including ACTs can be administered through NG tube 3. Sponging if hyperthermia 4. Nurse and/or MD to do regular assessments

FOLLOW UP Repeat clinical assessment every 2-4 hrs - If decrease of coma score -> 1. Assess seizures, 2. Hypoglycaemia 3. ↑Parasitaemia - Repeat labs/6h (in ideal conditions, ≠ in MSF settings) 4. Parasitaemia, 5. Hb/haematocrit 6. Glucose 7. Lactate

OTHER -Cerebral oedema: present?

- No evidence of benefit of Mannitol (even when radiologic evidence of edema (63% in one study of 126 adults in Bangladesh)) - Autopsy study: no association between coma and edema -Steroids: no benefit from use -Oxygen: if SatO2 <90% -Nitrous Oxide: some possible benefit (Epicentre study ongoing)

NEUROLOGICAL SEQUELAE The most common sequelae of Cerebral Malaria are: -hemiplegia -cortical blindness -aphasia -ataxia Predisposing factors for neurological sequelae are: -prolonged coma -protracted convulsions -severe anaemia -biphasic clinical course (convulsions-> coma -> recovery -> convulsions -> coma)

NEUROLOGICAL SEQUELAE II -Transient: 1. Psychosis: associated with the use of Mefloquine as treatment 2. Ataxia: can last months -Rapid improvement: 1. Cortical blindness 2. Aphasia -Persisting: 1. Hemiparesis 2. Extrapyramidal syndrome 3. Cognitive impairment