52. Malaria MB ChB July 29 2015.pptxfhjhsdhddsh

malaria

1. Malaria in Children – Overview Dalton Wamalwa 29.07.2015

2. Outline Introduction and Epidemiology Pathogenesis/pathophysiology Diagnosis : Clinical & laboratory Management & Prevention

3. Introduction Malaria is the most important parasitic disease o f man. Burden in Kenya: Malaria incidence: 3.7 million cases Malaria mortality 27000 deaths (2012) Most vulnerable children under five years and pregnant women

4. The malaria parasite Malaria is caused by parasite genus Plasmodium Plasmodium falciparum is the predominant species (98.2 % ) Almost all death s are caused by P. falciparum Benign forms : P.vivax , P. malariae , and P. ovale , P. knowlesi Vector : Anopheles (41 species in Kenya)

5. Life cycle A. Pre- erythrocytic stage Sporozoites injected : blood Within 45 minutes either cleared or enter hepatocyte B. Asexual liver stage Hepatic schizoint rupture C. Asexual blood stage Merozoites infect RBC in cycles Subset develop-gametocytes D: Sexual stage in mosquito * P. Falciparum B= 5 days , C = 48 hours Incubation about 10 -14 days

6. Malaria endemicity in Kenya (parasite rate 2-9 yr old) Holo-endemic (>75) H yper-endemic (50-74) Meso-endemic (11-49) Hypo-endemic (< 10)

7. Severe Malaria Clinical or laboratory evidence of vital organ dysfunction Patients suspected to have severe malaria should be treated with parenteral therapy. Lab results should not delay treatment

8. Clinical features of severe malaria Impaired consciousness including coma Prostration: generalized weakness, unable to sit, walk without assistance Multiple convulsions ; > 2 per 24 hours Deep breathing and respiratory distress Circulatory collapse (shock) Acute kidney injury, jaundice, abnormal bleeding Acute pulmonary oedema

9. Key Laboratory features Hypoglycaemia (< 2.2mmol/l) Metabolic acidosis (plasma HCO3< 15mmol/l); Severe normocytic anemia ( Hb < 5g/dl, PCV < 15% in children) Haemoglobinuria Renal impairment (  serum creatinine )

10. Pathogenesis of severe malaria

11. Severe Malaria : Cerebral malaria Diffuse but reversible encephalopathy Not seen in ANY other infection Cause of coma unknown – neuro-protective? Impaired Perfusion Low cerebral blood flow Cerebral anaerobic glycolysis Cytokines – TNF, IF, IL Nitric acid Inhibits neuro-tranmission Coma is NOT Caused by increased Intra-cranial Pressure

12. Severe Malaria : Acidosis Major cause of death in severe malaria Microvascular obstruction: leads to tissue anaerobic glycolysis - Failure of hepatic and renal lactate clearance Production of lactate by Plasmodium Worsened by dehydration and anemia Presents as: respiratory distress and/or d eep acidotic breathing

13. Severe Malaria : Anemia Destruction of parasitised RBC at merogony Increased destruction of non- parasitised RBC since all RBC become more rigid Splenic threshold lowered: removes large numbers of rigid RBC Shortened survival of RBC after splenic parasite removal Bone marrow dyserythropoiesis – days to wks

14. Severe Malaria : Hypoglycemia Increased peripheral demand for glucose: Tissue anerobic glycolysis Febrile illness – high metabolic rates Parasites use glucose Decreased supply of glucose Failure of hepatic glycogenolysis and glucuneogenesis Children : reserves 12 hr , adults > 2 days

15. Susceptibility to bacterial infection Increased incidence of severe bacterial infection: Pulmonary infections Urinary tract infections Severe malaria predisposes to severe gram negative sepsis May be difficult to distinguish on clinical grounds

16. Diagnosis of Malaria/severe malaria

17. Who is at risk for severe malaria ? In high-transmission areas, risk greatest among: Young children Visitors (any age) from non-endemic areas. In other areas, severe malaria more evenly distributed across all age groups. Risk is increased in the 2 nd -3 rd trimesters of pregnancy Patients with HIV/AIDS have increased risk

18. Diagnosis of Malaria Most important aspect is a high index of suspicion History of travel to endemic zones or recent blood transfusion Efforts should always be made to get parasitologic diagnosis. In absence or delay of microscopy in areas of high transmission treat on clinical grounds: Suspected severe malaria in all patients All Children < 5 yrs

19. Parasitological diagnosis of severe malaria Microscopy is the gold standard and preferred option for diagnosing malaria. In nearly all cases, examination of thick & and thin blood films will reveal malaria parasites. Thick films are more sensitive than thin films for detecting low density malaria parasitaemia

20. Low parasitemia in severe malaria Parasites in severe falciparum malaria are usually sequestered in capillaries and venules May not always be seen on a peripheral blood slide) Patients may present with severe malaria with very low peripheral parasitaemia. Case reports of malaria found at autopsy in cerebral blood vessels with smear negative

21. Role of Rapid Diagnostic Tests Based on antigen detection (from blood stage): Histidine rich proteins (HRP, Plasmodium lactate dehydrogenase , Aldolase Sensitivity and specificity approx 95% Useful in patients who have recently received treatment and have negative MPS RDTs cannot: be used to monitor the response to treatment, can remain positive for up to 4 weeks after clearance of parasitaemia. Provide information on parasite density

22. Approach to management

23. Management Principles: Severe Malaria H DU or ICU management protocol Effective anti- malarials Fluids Glucose supplements Safe Blood Anticonvulsants Monitoring Parental counseling Follow up

24. Kenya National Guidelines Uncomplicated Malaria First line treatment in all ages Artemether –lumefantrine Second line treatment: Dihydroartemisinin - piperaquine

25. Antimalarial therapy: severe malaria Artesunate injectable is the preferred treatment for severe malaria all ages High efficacy Rapid Effect Artemether (intramuscular) Quinine injectable (especially intravenous)

26. Supportive Management - Fluids Rapid fluid boluses are contraindicated in severe malaria resuscitation. Oral fluids preferred If unable to retain oral fluids use 5% dextrose and / isotonic saline (0.9%) maintenance fluids Dehydration- manage cautiously guided by urine output (target > 1ml/kg body wt/hour

27. Other causes of coma Make sure to look for other treatable causes of coma. Meningitis should be excluded by lumbar puncture otherwise presumptive therapy.

28. Hypoglycemia Hypoglycaemia should be corrected immediately :5ml/kg 10 % dextrose Followed with a slow intravenous infusion of 5ml/kg per hour of 10% or 10ml/kg per hour of 5% dextrose to prevent recurrence

29. Post discharge follow-up Severe anaemia and neurological complications important causes of mortality immediately after treatment Follow-up to monitor haemoglobin recovery Neurological involvement require longer follow-up.

30. Prevention I ndoor Residual Spraying (IRS) Sleeping under Insecticide-treated mosquito nets (ITNs) Prophylaxis in necessary situations Atovaquone / proguanil Mefloquine Vaccines : anti- sporozoite (Efficacy  45%) against severe malaria Wanes to 22% after 4 years

31. Questions

32. Case Study Kassim is a 2 year old who lives in Mombasa and has had normal development. He is brought to casualty with a history of fever (2 days) and two generalized tonic- clonic convulsions (3 hours ago). On examination he is febrile (39.5 o C) and is drowsy but responds to pain. What are the two most important diagnostic tests for this child ? a. Lumbar puncture b. Blood culture and sensitivity c. Full haemogram and peripheral blood film d. Cranial CT scan e. Thick smear for malaria parasites

33. Treatment decision Kassim’s blood slide shows heavy parasitemia. He is also now to be restless with deep sighing respiration. What is the most preferred drug to use? a. intramuscular quinine b. intravenous quinine c. sodium bicarbonate d. oral artemisinin lumefantrine e. intravenous artesunate

34. Major indicators of poor prognosis Age < 3 years Deep coma Decerebrate or decorticate rigidity , opisthotonus Clinical signs of organ dysfunction ( e.g.renal injury, pulmonary oedema ) Respiratory distress (acidosis) Shock Papilloedema

35. Treatment of severe P.falciparum Malaria The Africa Quinine versus Artesunate in Severe Malaria Trial, published on the Lancet, Nov. 8th, 2010

36. Findings (5425 children) Artesunate Quinine Number 2712 2713 Death 230 (8.5%) 297 (11%) Development of coma 3.7% 5.4% Development of Convulsions 8.3% 10.1% Hypoglycemia 1.8% 2.8% Long term neurologic sequel No differences

37. Interpretation Artesunate substantially reduces mortality in African children with severe malaria. Data strongly suggest that parenteral artesunate should replace quinine everywhere as treatment of choice for severe falciparum malaria.

38. Patho -physiology Cytokines Plasmodium leads to release of cytokines TNF, IL-1, IFN  : inflammatory – fever & malaise Prognostic value Cyto -adherence & Sequestration RBC with mature forms adhere to micro-vascular endothelium (starts 12 hrs after merozoite invasion) Cells remain stuck – do not re-enter circulation Thus RBC disappear from the circulation Red Cell deformability: Cells become more spherical Readily removed by the spleen