Malaria

Pharmacotherapeutics of Malaria

1. Malaria Dr. V. S. Swathi Assistant Professor

2. Definition Malaria is a life-threatening disease caused by parasites that are transmitted through the bites of female anopheles mosquito. It is preventable and curable

3. Epidemiology In the world, 219 million cases of malaria were found in 2017. Estimated deaths related to malaria were 4,35,000 In India, 6% of world malaria cases were found in 2017. Among them, 6% of cases leads to death

4. Types Malaria due to Plasmodium vivax It spreads across the globe and predominantly found in India It results to death and serious issues Malaria due to Plasmodium ovale It mainly found in tropical west african region it is rarest type of malaria because parasite resides in the host's body for extended periods, sometimes up to years after mosquito bite Malaria due to Plasmodium malariae It found in tropical and subtropical regions of central and south america, africa and south east asia It is a non lethal disease Malaria due to Plasmodium falciparam It found in south east asia, south america and africa Largest number of death are due to this type

5. Risk factors Live/ visit areas where disease is predominant Young children and infants Elders Pregnant women and their unborn children Travellers Poverty Lack of knowledge Little or no access to health care Patients with HIV Patient with immune suppression Patients receiving blood transfusion Lack of protective clothing Exposed sleeping accommodation Lack of immunisation Areas with stagnant water

6. Etiology Transmitted by female anopheles mosquito Caused by: Plasmodium falciparam Plasmodium vivax Plasmodium ovale Plasmodium malariae

7. Pathogenesis

8. Clinical Presentation Initial stage Non specific fever Chills or rigors Diaphoresis Malaise Vomiting Orthostatic hypotension Electrolyte abnormalities

9. Erythrocyte phase Prodrome: Headache Anorexia Malaise Fatigue Myalgia Non specific complaints Abdominal pain Diarrhoea Chest pain Arthralgia

10. Paroxym High fever Chills Rigors Cold phase Severe pallor Cyanosis of lips Hot phase High fever Sweating phase Follows hot phase by 2-6 hours where fever resolves

11. Marked fatigue Drowsiness Warm and dry skin Tachycardia Cough Severe headache Nausea Vomiting Abdominal pain Diarrhoea Delirium

12. Complications Lactic acidosis Hypoglycaemia Anaemia Acute renal failure Pulmonary oedema Thrombocytopenia Heart failure Cerebral congestion Seizures Coma Adult respiratory syndrome

13. Diagnosis Smear test Lab test Computed tomography Magnetic resonance imaging

14. Non Pharmacological Treatment Use of mosquito repellents Avoid travelling to malaria prone areas Cover body totally Use window screens Use insecticide- impregnated nets

15. Treatment algorithm

16. Drugs used in treatment of malaria Drug Category Mode of action Dose Adverse effects Chloroquine Anti malarial drug Active against erythrocyte form of plasmodium vivax, ovale and falciparam 300mg base once weekly, begin 1-2 weeks before travel and continue up to 4 weeks after travel for chemoprophylaxis 600mg base on first day then 300mg base 6 hours, 24 hours and 48 hours for uncomplicated chloroquine susceptible malaria Abnormal ECG Prolonged QT Amnesia Pruritis Retinopathy Hydroxychloroquine Anti malarial drug It prevents growth and replication of parasite by decreasing the pH of vacuole 310mg base once weekly, begin 1-2 weeks before travel and continue up to 4 weeks after travel for chemoprophylaxis 310mg base on first dose then 6 hours, 24 hours and 48 hours for uncomplicated chloroquine susceptible malaria Irritability Weakness Leucopoenia Thrombocytopenia Anaemia

17. Mefloquine Anti malarial drug It prevents growth and replication of parasite by decreasing the pH of vacuole 228mg base once weekly, begin 1-2 weeks before travel and continue up to 4 weeks after travel for chemoprophylaxis 648mg base on first dose then 456mg base 6 hours, 24 hours and 48 hours for Uncomplicated Plasmodium falciparam malaria Anxiety Difficulty in concentration Insomnia Tinnitus Vertigo Primaquine Anti malarial drug Disrupts plasmodium mitochodria 30mg base once weekly, begin 1-2 days before travel and continue up to 7 days after travel for chemoprophylaxis 30mg base orally once daily for 14 days Abdominal pain Arrhythmias Nausea Vomiting Visual disturbances

18. Atovaquone Anti malarial drug Inhibits electron transport chain in plasmodium 250mg four times daily for 3 days with food or milk for Uncomplicated chloroquine resistance malaria Abdominal pain Cough Diarrhoea Dyspnoea Fever Proguanil Anti malarial drug Inhibits parasites’ dihydrofolate reductase leads to decrease in DNA synthesis 100mg four times daily for 3 days with food or milk Uncomplicated chloroquine resistance malaria Abdominal pain Itching Diarrhoea Myalgia Fever Artemether Anti malarial drug Inhibit nucleic acid and protein synthesis in parasite 20mg four times daily for 3 days with food or milk Uncomplicated chloroquine resistance malaria Abdominal pain Anorexia Arthralgia Asthenia Fever

19. Lumafantrine Anti malarial drug Inhibit nucleic acid and protein synthesis in parasite 120mg four times daily for 3 days with food or milk Uncomplicated chloroquine resistance malaria Abdominal pain Anorexia Arthralgia Asthenia Fever Quinidine Anti malarial drug Inhibit formation of beta haematin(toxic product) from parasite leads to decrease in digestion of RBC from parasites 6.25mg/kg for 1-2 hours then 0.0125mg/ kg/ min for about 24 hours for Severe malaria Abdominal pain Diarrhoea Anorexia Light headedness QT prolongation Doxycycline Tetracycline Inhibit protein synthesis in parasites 100mg once daily for 7 days for Uncomplicated Plasmodium falciparam malaria Anorexia Diarrhoea Dysphagia Enterocolitis Teeth discolouration

20. Resources https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6607595/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122616/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6122616/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030775/ https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5714960/