MALARIA presentation, transmission and treatment-pptx

Malaria

1. MALARIA

2. PRESENTER: THEMBO SIMON SUPERVISOR: Dr. OBURU

3. Outline Introduction Epidemiology Etiology and transmission Pathogenesis Clinical manifestations Diagnosis Complications Differential diagnosis Treatment Prevention

4. INTRODUCTION Malaria is a life threatening disease caused by parasites that are transmitted to people through the bites of infected female Anopheles mosquitoes. Severe malaria remains a major cause of pediatric hospital admission across Africa. Children aged under 5 years are the most vulnerable group affected by malaria cases and death in Africa (WHO, 2020).

5. Definition Malaria : An acute febrile illness caused by infection with malaria parasites. Illness can range from mild disease to a severe life-threatening illness. Uncomplicated malaria : is when malaria symptoms are present but no clinical or laboratory signs to indicate severity –Danger signs . Severe malaria ( complicated ) is a malaria illness that is serious enough to be an immediate threat to the life of the patient . Cerebral malaria : is defined as the presence of coma in a child with P. falciparum parasitemia .

6. Epidemiology Malaria is endemic through most of the tropics and continues to cause unacceptably high levels of disease and death. Of approximately 3.4 billion people world-wide who are exposed annually, WHO states that there were 198 million cases of symptomatic malaria in 2013. An estimated 584,000 deaths from malaria in 2013. Estimated malaria mortality rates decreased by 53% between 2000 and 2013 in children aged under 5 years ( WHO, 2014) Latest World Malaria Report(2021) recorded 241 million cases in 2020 with 627,000 deaths Uganda loses around 5,000 people due to malaria and 12 million cases are registered annually. The Global priority is to decrease the burden of disease and death while retaining the long term vision of malaria eradication.

7. Malaria: the case of Uganda Uganda has made tremendous progress in implementing key malaria control measures, in particular; distribution of insecticide-impregnated bed nets, indoor residual spraying of insecticides, utilisation of artemisinin -based combination therapy to treat uncomplicated malaria, provision of IPT for pregnant women, subsidising cost of some antimalarial medication, etc. EPICENTRE Currently Namutumba district is the epicentre of malaria, where the health ministry reported that close to 10 people die weekly due to malaria. MOH has confirmed the existence of genetic markers for artemisinin resistance in the country. Be on the look out for a need to switch to quinine

8. Aetiology: Plasmodium Falciparum - 99% Plasmodium Malariae Plasmodium Ovale Plasmodium Vivax Plasmodium Molesi Knowlesi Transmission: A bite from an infected female Anopheles mosquito. In rare occasions, through blood transfusion or contaminated needles. Via the placenta from mother to child (vertical transmission).

9. Pathogenesis (2/6)

10. Life cycle The life cycle of malaria parasite consists of following phases: Sexual cycle : in female anopheles mosquito, definitive host Asexual cycle : in human, as intermediate host. Sporozoites are the sexual form of the parasite. When the infected female anopheles mosquito bites the human then the sporozoites enter the human along with the saliva of the mosquito. Within 30min they enter the parenchymal cells of the liver , where during next 10 - 14 days, they undergo pre- erythrocytic stages of development and multiplication.

11. The life cycle of malaria parasite consists of following phases: 1. sporozites in saliva of female anopheles mosquito injected the man blood by the mosquito bites invade the liver cells where they grow and multiply. in this stage they do not attack R.B.C and after injection first enter the liver therefore this stage is called pre- erthrocytes stage . the infected liver cells is called schizont . rupture and release merozoites in to the blood

12. Cont, Following mitotic replication of its nucleus, the parasite is termed as schizont . At last the parasites rupture the liver cell and merozoites are released The merozoites from the liver cell then bind to or enter the RBC and further develops into trophozoites . The mulitplication here results to Erythrocytic schizont . S o me m erozoites of erythr o cytic s c h i z on y d evelop into m a l e a n d female gametocytes known as microgamates and macrogamates . T h ey are s ex u al form and are fo u n d in p er i ph er a l b lo o d .

13. Cont, Some of the sporozoites also, on entering into the liver cells, do not undergo asexual multiplication but enter into a resting phase called hypnozoite The sexual cycle of malaria parasites actually starts in the human host by the formation of gametocytes which are then transferred to mosquito for further develoment . In the midgut of the mosqito , one microgametocyte develops into 4 to 8 thread like filamentous structures named microgamates . From one microgamate only one microgamate is formed

14. Cont, T h e fe r t i l i z a t i o n occurs, and the gam a te is kno wn as z y g ote . The zygote matures into an ookinete and it further develops into an oocyts . An oocyts mature and it increases in size and a large no of sporozoites develop inside it. The oocyts rupture and releases sporozoites in the body cavity of mosquito. The sporozoites are distributed to different organs of the mosquito and they have a special predilection for salivary glands. The mosquito is now capable of transmitting the infection to man.

15. Clinical manifestations Like adults, children are asymptomatic during the initial phase of infection, the incubation period of malaria infection. The usual incubation periods are : 9-14 days for P. falciparum , 12-17 days for P. vivax *, 16-18 days for P. ovale , and 18-40 days for P. malariae .

16. Classification of malaria Uncomplicated malaria Complicated/severe malaria.

17. Uncomplicated malaria. Common symptoms/signs of uncomplicated malaria Fever: above 37.5°C (taken from the axilla ) or history of fever. Loss of appetite, mild vomiting, diarrhoea Weakness, headache, joint and muscle pain Mild anaemia (mild pallor of palms and mucous membranes); occurs commonly in children. Mild dehydration Enlarged spleen (in acute malaria it may be minimally enlarged, soft and mildly tender)

18. Complicated malaria.

19. Complicated malaria.

20. Complicated malaria.

21. Manifestation Mechanism Respiratory distress: Metabolic acidosis Cardiac failure Co-existent pneumonia Sequestration of parasites in lung Increased central respiratory drive in cerebral malaria Clinical signs are flaring of ala nasi , intercostal recession, sub-costal indrawing, increased respiratory rate, etc. Pulmonary oedema Excessive fluid replacement or sequestration of parasites in the lung. Metabolic acidosis; especially lactic acidosis Increased production of lactate as a result of reduced oxygen delivery to the tissues. Sequestration in the liver causes reduced hepatic blood flow, function and raised lactate; Cytokines cause lactate production Malaria parasites produce lactate; Renal impairment Other acids e.g. ASA and herbal medications.

22. Anaemia Destruction of parasitised cells (haemolysis) Destruction of non- parasitised cells Bone marrow suppression Bleeding, renal failure Acute kidney injury More common in non-immune adults More common with low blood pressure or shock Haemoglobinuria Spontaneous or after quinine: massive intravascular hemolysis Jaundice Haemolysis (↑ unconjugated bilirubin) Hepatic dysfunction Shock Due to inadequate cardiac output Concurrent bacteremia Spontaneous bleeding Reduced platelet count (thrombocytopenia) Disseminated intravascular coagulation

23. A delay in diagnosis and initiation of appropriate treatment is dangerous!! 1) Giemsa -stain, thick and thin blood films should be examined whenever malaria is suspected [The gold standard] 2) Where microscopy is not feasible or may be delayed, a positive rapid diagnostic test (RDT) is diagnostic (Based on anti-body to histidine-rich protein-2 (PfHRP2), parasite LDH (pLDH), or Plasmodium aldolase) ALWAYS REMEMBER! A positive B/S does not mean that malaria is the only cause of severe illness. Look-out for other possible causes. A negative BS does not rule-out the possibility of severe malaria. If symptoms are suggestive, treatment should be initiated and a repeat slide is necessary. Laboratory diagnosis of malaria

24. If blood smears do not reveal the diagnosis, then a PCR-based test for Plasmodium nucleic acids or an ELISA test for a protein specific for P. falciparum can be useful. Blood glucose: with altered consciousness, confusion, convulsions. Full blood count: Hb level , leucocytosis in pyogenic infections, leucopenia for typhoid and viral infections, thrombocytopenia for profound intravascular coagulation. Blood grouping and cross-matching HIV serology and other viral studies where necessary Serum electrolytes Blood cultures and sensitivity Urinalysis Blood gases , Ph. and anion gap . Rule out haemoglobinopathies e.g. sickle cell disease. LFTS: to differentiate from hepatitis. Serum creatinine, BUN Lumbar puncture to exclude bacterial meningitis in a patient with severe malaria and altered level of consciousness or in coma, in the absence of contraindications Chest X-ray Abdominal ultrasound Other Investigations

25. Management of Uncomplicated Malaria. supportive management Treat as out patient and educate mother for danger signs Fever management, administer an antipyretic fever, the recommended paracentamol 15mg/kg TDS, is preferred over non steroidal ant -inflammatory (NSAIDS). Other mechanical methods for reducing temperature include exposure, fanning or tepid sponging. Encourage adequate fluids and nutrition. Fallow-up date and re-test BS.

26. Management of uncomplicated Malaria . Artemisin based combination therapy (ACT) All patients: including children <4 months of age and pregnant women in 2nd and 3rd trimesters F irst line medicine: Artemether / Lumefantrine AL. ( 20mg/120mg ) 5-14kg (<3yrs )1 tab(140mg) twice for 3days. 15-24kg (4-7yrs) 2 tabs(280mg) twice for 3 days. 24-34kg ( 7-12 yrs.) 3 tabs(420mg) twice for 3 days. > 35 kg ( > 12 yrs ) 4 tabs(560mg) twice for 3 days.

27. Management. First line alternative Artesunate / Amodiaquine Dose of artesunate 5–11 months: 25 mg (½ tab) once for 3 days 1–6 years 50: mg (1 tab) once for 3 days 7–13 years :100 mg (2 tabs) >13 years: 200 mg (4 tabs) once for 3 days Note: Do not use artesunate alone, give with amodiaquine tabs Dosage of amodiaquine 3 5–11 months 76 mg (1/2 tab) once for 3 days 1–6 years 153 mg (1 tab) once for 3 days 7–13 years 306 mg (2 tabs) once for 3 days >13 years 612 mg (4 tabs) once for 3 days Note: Do not use amodiaquine alone, use with artesunate tabs.

28. Management. Second line medicine : Dihydroartemisin / Piperaquine OR quinine tablets Dosage of dihydroartemisin / Piperaquine ( 40/320mg) tablet 3.5–9.9 kg (6 month– 1 year) 0.5(180mg) tab for 3 days 10–20 kg (2–7 years) 1 tab(360mg) for 3 days 20–40 kg (8–13 years ) 2 tabs(720mg) for 3 days ≥ 40kg ( ≥ 14 years) 3 tabs(1080mg) for 3 days NOTE : The dosage of quinine is 30mg/kg in three divided dose of 10mg/kg for 7 days.

29. Management of complicated Malaria

30. Common in children <3 years; those convulsing; in profound coma; Hyperparasitaemia. Low blood glucose: <2.2 mmol/L (< 45 mg/dl) Or <3.0 mmol/L (< 54 mg/dl) in a severely malnourished child. Rx threshold: <3 mmol/L in <5 yrs. and <2.2 mmol/L in older children. Pathophysiology Pre-treatment: Impaired gluconeogenesis. Accelerated metabolism. Reduced food intake. Parasite glucose consumption. During treatment: Quinine stimulates insulin secretion. Rapid infusions of quinine (>10mg/kg/hour) can precipitate hypoglycaemia. MANAGEMENT Check random blood sugar before and 30 minutes after correcting hypoglycaemia. Note: If blood glucose cannot be measured and hypoglycaemia is suspected, give glucose. If patient is convulsing or in coma, assume hypoglycaemia. Give the following: 5ml/kg of 10% dextrose as a bolus If no IV dextrose, mix a sugar solution and give orally or by NG tube if unconscious. Continue feeding the patient orally or through NG-tube to prevent hypoglycaemia. May administer calculated maintenance fluids as D10% in N/S or R/L (D50%:N/S or R/L, ratio-1:4). Hypoglycaemia

31. Hb level ≤5 g/dl This is usually due to: Haemolysis . Reduced erythropoiesis . Reduced RBC life span. Sequestration of the red blood cells in the spleen and liver. MANAGEMENT 10-15 ml/kg of packed cells or 20 ml/kg of fresh whole blood Administered over 3–4 hours . Monitor vitals closely during transfusion. Consult guidelines on blood transfusion in special situations e.g. severe acute malnutrition in children. If there is any evidence of fluid overload due to the blood transfusion, give IV furosemide (1–2 mg/kg) up to a maximum total dose of 20 mg. After the transfusion, if the Hb remains low (≤5g/dl), repeat the transfusion. Continue with oral haematinics for 12 weeks. Advise parents/carers on diet/nutrition. Deworm child if > 1 year. Also transfuse less severely anaemic children with Hb of 5–6 g/dl with any of the following clinical features: Clinically detectable dehydration, shock, impaired consciousness, heart failure, deep- laboured breathing, very high malaria parasitaemia (> 10% of red cells with parasites). Severe anaemia

32. Thrombocytopenia is common in falciparum malaria, often without other coagulation abnormalities and resolves soon after treatment. Presents with; bleeding from gums, epistaxis, petechiae, subconjuctival hemorrhage, and sometimes gastro-intestinal bleeding may occur. MANAGEMENT Transfusion with fresh whole blood (20mls/kg), Fresh frozen plasma (10mls/kg), Platelets (0.2mls/kg), Cryoprecipitate Administer vitamin K. Rare This is due to: Deposition of hemoglobin in the renal tubules. Reduced renal blood flow. Acute tubular necrosis. MANAGEMENT Exclude pre-renal causes e.g. dehydration Appropriate fluid resuscitation. Diuretics e.g. furosemide. Monitor fluid input/output, urine sodium. Stop drugs which can further impair renal function. Peritoneal dialysis (hemofiltration or haemodialysis if available) based on severity. Spontaneous bleeding Acute kidney injury

33. Hyperpyrexia Axillary temperature ≥39.5 o C or Rectal temperature ≥40.0 o C. MANAGEMENT Paracetamol by mouth or anal suppository (15 mg/kg/dose 4-6 hourly) Remove clothes and do tepid sponging, fanning (prevent febrile convulsions in children). Dehydration MANAGEMENT Children 2-11 months: 30mls/kg in 1 st hour, then 70mls/kg in the next 5 hours. Children 12 months – 5 years: 30mls/kg in 1 st 30 minutes, then 70mls/kg in next 2.5 hours. Monitor hydration. Do not overload with intravenous fluid. Consult guidelines for fluid resuscitation in other special situations. Metabolic acidosis MANAGEMENT Exclude/treat hypoglycaemia, dehydration and gram negative septicaemia. Correct with crystalloid e.g. N/S or R/L 20ml/kg IV over 30mins, if Hb ≥5g/dl. Blood transfusion if Hb < 5 g/dl . Give 100% oxygen. Hemofiltration or hemodialysis, if severe .

34. Convulsions MANAGEMENT Maintain airway; slow IV diazepam (0.3mg/kg, maximum 20mg) or intra-rectally (0.5mg/kg). Monitor breathing. If convulsions reccur, repeat dose to maximum 3 doses. Recovery position Use Phenobarbitone, phenytoin (for repetitive convulsions). Look for and treat causes of convulsion(s), including hypoglycaemia. If temperature is ≥ 38.5 °C, give a dose of Paracetamol. Aspiration Pneumonia MANAGEMENT Clear airway by suction, place patient in left lateral position or 30-45 o head-up, give oxygen, broad spectrum antibiotics (to include antibiotic cover for anaerobes). Haemoglobinuria MANAGEMENT Rehydrate patient. May be triggered by certain drugs in G6PD deficiency. Assess for anaemia and transfuse if necessary.

35. Pulmonary oedema MANAGEMENT Prop up patient to 45°, give 100% oxygen and diuretics ( furosemide 1-2mg/kg), stop IV fluids. Intubation and PEEP or CPAP in life-threatening hypoxemia. Shock MANAGEMENT Correct hemodynamic disturbance using IV fluids; R/L or N/S - 20ml/kg boluses. Shock due to malaria (algid malaria) may be associated with gram negative septicaemia . Start parenteral broad-spectrum antibiotics , do blood cultures and sensitivity, and adjust treatment accordingly. Coma MANAGEMENT ABCDs, RBS or assume hypoglycaemia and give bolus of IV 10% dextrose, Insert NG tube for medications/feeding/prevention of aspiration, Insert urethral catheter, maintain dry bed, monitor fluid input/output, vitals, recovery position, 2hourly turning in bed, other supportive treatment. Look for, and treat cause! Intubate if necessary

36. Specific treatment - medication

37. An overview of the specific treatment of severe malaria Parenteral artesunate is the current drug of choice for the treatment of severe P. falciparum malaria. Dose 3mg/kg at 0, 12, 24hrs <20kg 2.4mg/kg at 0,12, 24hrs >20kg If it is not available, parenteral quinine or artemether should be used. Note: Give antimalarial agents by the parenteral route until the patient can take oral medication but for a minimum of 24 hours, even if the patient can tolerate oral medication earlier. Complete treatment with a full course of oral artemisinin -based combination therapy (ACT), such as; ) Dihydroartemisinin + Piperaquine (e.g. P- alaxin , D- artepp ) or Artemether + Lumefantrine (e.g. Coartem , Lumartem , Artefan Artesunate + Amodiaquine Artesunate + Sulfadoxine – Pyrimethamine

38. IV/IM Quinine dihydrochloride 300mg/ml, 2ml ampoule. Dose: 10mg/kg of quinine salt, 8hourly in 10ml/kg of 5% dextrose for IV infusion over 2-4hours . The infusion rate should not exceed a total of 5 mg/kg/hour of quinine dihydrochloride salt. If IV administration not possible, give same dose of quinine, diluted for IM use, 8hourly. How to mix and administer IM Quinine: Add 4mls of water for injection to 2ml ampoule of Quinine (600mg), to get 6ml, each ml containing 100mg Quinine. You require 0.1ml/kg. If total dose >300mg (>3mls), divide into 2 and inject ½ in each thigh, NOT buttock! QUININE

39. Route: Intra-muscular (IM) Dose: 3.2 mg/kg on admission then 1.6 mg/kg daily until the patient can take oral medication. Use a 1-ml tuberculin syringe to give the small injection volume. As absorption of Artemether may be erratic, it should be used only if Artesunate or Quinine is not available. ARTEMETHER

40. Common errors in the management of severe malaria Failure or delay of referral Errors in fluid and electrolyte replacement Delay in starting antimalarial treatment Dosage not correctly calculated Unjustified cessation of treatment before completion Failure to control the rate of IV infusion Failure to identify and treat acidosis, hypoglycaemia , severe anaemia , pulmonary oedema , etc. Failure to switch patients from parenteral to oral treatment at appropriate time Failure to review patient with deteriorating condition Failure to pass NG tube when indicated Failure to cover with antibiotics when indicated

41. Malaria Prophylaxis Not recommended for all those living in a highly endemic area like Uganda. However, it is recommended for certain high-risk groups but is not 100% effective. Sicke cell disease (Chloroquine, Child : 5 mg (base)/kg weekly or Sulphadoxine Pyrimethamine (SP). People living with HIV : Cotrimoxazole daily as per national guidelines. Non-immune visitors/tourists : Mefloquine, Child : 5 mg/kg once weekly .

42. Prevention Give effective treatment and prophylaxis : Eliminate parasites from the human population by early diagnosis and effective treatment Protect vulnerable groups with chemoprophylaxis Reduce human-mosquito contact Malaria vaccine-RTS , S/AS01 MALARIA VACCINE which is a 4dose schedule for children living in regions of moderate to high transmission Control mosquito breeding sites Give public health education on the above measures.

43. Meningitis Encephalitis Septicaemia Bacterial pneumonia Typhoid fever Brucellosis Acute gastroenteritis Urinary tract infection African trypanosomiasis Viral illness e.g. measles, yellow fever Other viral hemorrhagic fevers Seizure disorder Tetanus, etc . Differential diagnoses Possible long-term complications of malaria Neurocognitive sequelae; may take the form of cerebellar ataxia, hemiparesis, speech disorders, cortical blindness, behavioural disturbances, hypotonia or generalized spasticity. Burkitt’s lymphoma Hyper-reactive malaria splenomegaly

44. References Nelson Textbook 21 st edition Uganda clinical Guidelines 2023 WHO report, March 2020 Up-to-date- 2024 WHO, 2013, Pocket book of hospital care for children.