SEVERE MALARIA IN CHILDREN-NEW TREATMENT GUIDELINE DR ABUBAKAR USMAN FMC BIDA 24th August 2013

OUTLINE INTRODUCTION DEFINITION EPIDEMIOLOGY COMPONENTS OF SEVERE MALARIA COMPLICATIONS TREATMENT NEW RECOMMENDATION ARTESUNATE VS QUININE CONCLUSION

INTRODUCTION Malaria has remained a major public health problem in Nigeria children under the age of five and pregnant women are still the most affected. More than 60% outpatient visits in Nigeria is due to malaria. The disease has impacted negatively on the economy with about 132 billion Naira lost to the disease as cost of treatment and loss in man-hours. Every year, there are about 500 million clinical attacks of malaria. Of these, 2-3 million are severe and about 1 million people die (about 3000 deaths every day).

INTRODUCTION accounts for 10-30% of all hospital admissions 80% of all malaria cases occur in tropical Africa where the disease accounts for 10-30% of all hospital admissions is responsible for 15-25% of deaths in children aged <5 years - about 800,000 child deaths every year. kills an African child every 30 seconds

INTRODUCTION cont’d key strategy to control malaria is effective case management. malaria treatment has been based mainly on clinical diagnosis which is presumptive The Drug Therapeutic Efficacy Tests (DTET) on chloroquine and Sulphadoxine- pyrimethamine in 2002 Artemisinin based Combination Therapy (ACTs) as treatment of uncomplicated malaria was introduced in 2005 A 2nd DTET 2009

DEFINATIONS Uncomplicated malaria: Symptomatic infection with malaria parasitaemia without signs of severity and/or evidence of vital organ dysfunction. Severe falciparum malaria: Acute falciparum malaria with signs of severity and/or evidence of vital organ dysfunction.

EPIDEMIOLOGY Malaria transmission is stable in Nigeria. Children under the age of five, pregnant women and nonimmune visitors from non- endemic areas are particularly more susceptible than the general population.

THE CLINICAL COURSE OF MALARIA. Following a bite by an infected mosquito, many people do not develop any signs of infection. If infection does progress, the outcome is one of three depending on the host and parasite factors. Asymptomatic parasitaemia (clinical immunity) Acute, uncomplicated malaria Severe malaria

1. Asymptomatic parasitaemia This is usually seen in older children and adults who have acquired natural immunity to clinical disease as a consequence of living in areas with high malaria endemicity. There are malaria parasites in the peripheral blood but no symptoms. These individuals may be important reservoirs for disease transmission. Some individuals may even develop anti-parasite immunity so that they do not develop parasitaemia following infection.

2. Simple, uncomplicated malaria This can occur at any age but it is more likely to be seen in individuals with some degree of immunity to malaria. The affected person, though ill, does not manifest life- threatening disease. Fever is the most constant symptom of malaria. It may occur in paroxysms when lysis of red cells releases merozoites resulting in fever, chills and rigors. Children with malaria waiting to be seen at a malaria clinic in the south western part of Nigeria. Identifying children with severe malaria, and giving them prompt treatment, is a major challenge when large numbers attend clinics.

Other features of uncomplicated malaria Vomiting Diarrhoea – more commonly seen in young children misdiagnosed as viral gastroenteritis Convulsions – commonly seen in young children. Malaria is the leading cause of convulsions with fever in African children. Pallor Jaundice Anorexia, Cough, Headache, Malaise, Muscle aches, Splenomegaly Tender hepatomegaly These clinical features occur in “mild” malaria. However, the infection requires urgent diagnosis and management to prevent progression to severe disease.

Peculiarity of paediatric age-groups and malaria. Birth-6months- not prone to malaria. Trans-placental IgG acquired from the mother. Over-protection Foetal haemoglobin. 6months-5years-Highly prone to malaria. Maternal antibodies level begin to wane down by 6months Inability to fully express self and seek help promptly. Loss foetal haemoglobin. Increased activity and reduced protection. Older children- less prone to severe malaria. Acquired (herd) immunity. Can express themselves and get help more promptly. Recurrent infections leads to acquired immunity.

ASSESSMENT AND MANAGEMENT OF SEVERE MALARIA Definition A patient has severe malaria when there is P. falciparum asexual parasitaemia and no other confirmed cause of their symptoms, in the presence of one or more of the following clinical or laboratory features: Nearly all severe disease and the estimated >1 million deaths from malaria are due to P. falciparum. it is frequently a fatal disease.

Who are the people at risk for severe malaria? Children < 5 years Pregnant women People returning or coming to Nigeria after living in malaria free areas People who have had splenectomy

Clinical manifestations Prostration -i.e. generalized weakness or inability to sit, stand or walk without support Impaired consciousness (confusion or drowsiness or coma) Respiratory distress (difficulty in breathing, fast deep breath) Multiple convulsions (>2 generalized seizures in 24 hrs with regaining of consciousness)

Clinical manifestations Circulatory collapse (shock) Pulmonary oedema (respiratory distress /radiology) Abnormal bleeding (disseminated intravascular coagulopathy) Jaundice (yellow discoloration of the eyes) + +++ Haemoglobinuria (Coca-Cola coloured urine)

Laboratory parameters Hyperparasitaemia- smear exceeding 5% of erythrocytes Severe anaemia ( Hb <5 g/dl) Hypoglycaemia (Less than 40mg or 2.2 mmol/l) Renal failure (Urine output of less than 400 ml in 24 hours or <12ml/kg per 24 hours in children and a serum creatinine of more than 265 µmol/l (> 3.0 mg/dl), failing to improve after rehydration)

Practical issues in Management of Uncomplicated Malaria Antipyretic measures If temperature is > 38.5°C, give Paracetamol 10 - 15 mg/kg in children every 6 – 8 hours or when necessary or advice to tepid sponge and avoid over clothing. Persistent Vomiting If a patient vomits the medicine within 30 minutes, repeat the dose. If this is vomited again and the vomiting becomes persistent, the patient should be considered as having severe malaria and managed accordingly. Febrile Seizures If a patient has a seizure and does not recover within 30 minutes from that seizure, it should be considered as severe malaria.

ALGORITHM FOR MANAGEMENT OF SEVERE MALARIA Consciousness not impaired Give ACT and Treat main complications Oral medication not feasible, treat as severe malaria Impaired Consciousness IV/IM Artesunate or IM Quinine

Specific Antimalarial Treatment Artesunate Recommended Dosages: Give 2.4 mg/kg body weight IV or IM stat, repeat after 12 hours and 24 hours, then once daily for 6 days. However once patient regains consciousness and can take orally, discontinue parenteral therapy and commence full course of recommended ACT.

Specific Antimalarial Treatment cont’d Quinine Recommended dosage: Intravenous quinine Children: Give 20 mg/kg of Quinine dihydrochloride salt as loading dose diluted in 10 ml/kg of 4.3% dextrose in 0.18% saline or 5% dextrose over a period of 4 hours. Then 12 hours after the start of the loading dose, give 10 mg salt /kg infusion over 4 hours every 8 hours until when patient is able to take orally. Change to quinine tablets 10 mg/kg 8 h

Why we need to make the switch Effectiveness – Artesunate is the most effective treatment Administration – Artesunate is easy to administer Regulatory – WHO and NMCP strongly recommend artesunate Cost – Switching from quinine or artemether is cost-effective

Artesunate vs Quinine in severe malaria Effectiveness A study of over 5,000 African children showed a 22.5% relative mortality reduction for artesunate vs. quinine Almost 200,000 lives could be saved annually if all global cases of severe malaria were treated with artesunate Administration Compared to quinine, artesunate requires fewer doses, reduces risk of convulsions, coma, or hypoglycemia, and can be administered more rapidly (IV or IM) Compared to artemether, artesunate is absorbed more easily and breaks down easily to it’s active metabolic dihydroartemisinin

key recommendations provided in the updated guidelines Prompt parasitological confirmation by microscopy or RDTs is recommended in all patients suspected of malaria before treatment. Treatment solely on the basis of clinical suspicion should only be considered when a parasitological diagnosis is not accessible. Artemisinin-based Combination Therapies (ACTs) are the recommended treatments for uncomplicated P. falciparum malaria. ACTs recommended for use in Nigeria Artemether-lumefantrine, Artesunate- amodiaquine,

key recommendations provided in the updated guidelines Artemisinin and its derivatives should not be used as monotherapy in the treatment of uncomplicated malaria Oral Quinine is the recommended medicine for the treatment of uncomplicated malaria in the first trimester and in children less than 5kg, however, ACTs can be used under supervision by the health care provider

key recommendations provided in the updated guidelines Intravenous artesunate is preferred for the treatment of severe P. falciparum malaria Parenteral quinine or artemether is an acceptable alternative if artesunate is not available. Parenteral antimalarial medicines should be administered for a minimum of 24 hours once started

key recommendations provided in the updated guidelines In settings where complete treatment of severe malaria is not possible, patients should be given pre-referral treatment and referred immediately to an appropriate facility for further treatment. The recommended pre-referral treatment options include any of these; artesunate IM or rectal, and quinine IM.

CONCLUSION “The antimalaria medicines recommended for the treatment of severe malaria in Nigeria is Intravenous or intramuscular Artesunate. Where this is not readily available, intravenous or intramuscular quinine, intramuscular artemether can be used as alternative”. National Guidelines for Diagnosis and Treatment of Malaria, Federal Ministry of Health, March 2011