Malaria remains a major global health problem, infecting over 240 million people annually and killing over 1 million, mostly children in Africa. It is caused by Plasmodium parasites and transmitted via mosquito bites. Diagnosis and treatment of both uncomplicated and severe malaria is discussed. Artemisinin-based combination therapies (ACTs) are the recommended treatments. For severe malaria, artesunate is the treatment of choice due to its superiority over quinine in clinical trials. Malaria control efforts aim to expand access to effective prevention and treatment.

1. MALARIA UPDATE Malaria Update

2. Why is Malaria important? Affects >2400 million people, over 40% of the world's population, in more than 100 countries. Every year 300 million to 500 million people suffer from this disease (90% of them in sub-Saharan Africa, two thirds of the remaining cases occur in six countries- India, Brazil, Sri Lanka, Vietnam, Colombia and Solomon Islands) About 1.5 million to 3 million people die of malaria every year (85% of these occur in Africa)

3. Cont… One child dies of malaria somewhere in Africa every 20 sec, and one malarial death occurs every 12 sec somewhere in the world. Estimated annual expenditure on malaria research, prevention and treatment: US$84 million/year

4. Malaria Kills more people than AIDS Malaria kills in one year what AIDS kills in 15 years For every death due to HIV/AIDS there are about 50 deaths due to malaria To add to the problem is the increasing drug resistance to the established drug. Continues to be most important cause of fever and morbidity in the world.

5. Malaria Name is derived from Italian word Mal’ aria or bad air

6. Malaria Human Malaria is caused by one of protozoan parasites: Plasmodium falciparum Plasmodium vivax Plasmodium ovale Plasmodium malariae Plasmodium knowlesi- forested regions of South East Asia Malaria is transmitted through the bite of an infected female Anopheles mosquito

8. Life cycle of malarial parasite

9. Malaria Diagnosis & Treatment

10. Uncomplicated Malaria Defined as symptomatic malaria without signs of severity or evidence ( clinical or laboratory )of vital organ dysfunctional Suspected mostly on the basis of fever or a history of fever Other signs and symptoms include : Headache Fatigue Abdominal discomfort Muscle and joint aches Anorexia Vomiting

11. Severe Malaria Manifestations of severe malaria include: Cerebral malaria, with abnormal behavior, impairment of consciousness, seizures, coma, or other neurologic abnormalities Severe anemia due to hemolysis Hemoglobinuria Pulmonary edema Abnormalities in blood coagulation and thrombocytopenia Cardiovascular collapse and shock

12. Parasitological diagnosis of Malaria Prompt parasitological confirmation by microscopy or alternatively by RDTs is recommended in all patients suspected of malaria before treatment is started. Note: Treatment solely on the basis of clinical suspicion may be considered in areas of high transmission where parasitological diagnosis is not available or is likely to delay treatment, particularly in high risk groups such as: in severe malaria cases, in children under 5 yrs of age and in pregnant women. * Update in 2010 Revised Guidelines

13. Malaria treatment : available drugs Quinine. Chloroquine. Artemesinin products eg Artemether, artether, artesunate. Mefloquine. Antibiotics eg doxycycline, clindamycin, azithromycin.

14. More choices means more confusion !!!

15. WHO-Current and Future directions “ Drug management of malaria” “ Malaria endemic countries which are experiencing high levels of resistance to currently used anti-malarial drugs as monotherapy are advised to switch over to combination therapy ”

16. Treatment of Uncomplicated P.Falciparum Infection The treatment of choice for uncomplicated falciparum malaria is a combination of two or more antimalarial medicines with different mechanisms of action. ACTs are the recommended treatments for uncomplicated falciparum malaria. The artemisinin derivative components of the combination must be given for at least three days for an optimum effect.

17. ACTs Currently recommended by the WHO : Artemether-lumefantrine Artesunate + Amodiaquin Artesunate + Mefloquine, Artesunate + sulfadoxine–pyrimethamine. Dihydrortemisinin + piperaquine Artemesinin –based combination therapies should be used in preference to sulfadoxine-pyrimethamine (sp) + amodiaquine (aq)

18. 2 nd line antimalarial treatment Alternative ACT known to be effective in the region Artesunate+tetracycline/doxycycline/clindamycin, any of these combinations should be given for 7 days Quinine (10mg/kg 3 times daily) + tetracycline(250mg qid)/doxycyline (100mg bd)/clindamycin(450mg tds), any of these combinations should be given for 7 days

19. Treatment of Severe P.Falciparum Severe malaria is a medical emergency . after rapid clinical assessment and confirmation of the diagnosis, full doses of parenteral antimalarial treatment should be started without delay with any effective antimalarial first available. For adults, artesunate 2.4 mg/kg body weight iv or im given on admission (time = 0), then at 12 h and 24 h, then once a day is the recommended treatment. Quinine is an acceptable alternative if parenteral artesunate is not available: quinine 20 mg salt/kg body weight on admission (iv infusion or divided im injection), then 10 mg/kg body weight every 8 h; infusion rate should not exceed 5 mg salt/kg body weight per hour.

20. Artemesinine or Quinine for severe falciparum ?? WHO view point : “ Artesunate is the treatment of choice for adults with severe malaria in view of a recent multicentric trial in which mortality in the Artesunate group was reduced by 34.7% as compared to Quinine group”.* *SEAQUAMAT , Lancet , 2005

21. Artemisinin Also known as qinghaosu, has been used in China for the treatment of fever for over a thousand years Potent and rapidly acting blood schizontocide and is active against all Plasmodium species Unusually broad activity against asexual parasites, killing all stages from young rings to schizonts. In P. falciparum malaria also kills the gametocytes which are otherwise only sensitive to primaquine.

22. Side effects? Safe and remarkably well tolerated . Git disturbance, dizziness, tinnitus, reticulocytopenia, neutropenia, elevated liver enzyme values, and ECG abnormalities including bradycardia and prolongation of the QT interval (studies have not found any ECG abnormalities)

23. QUININE Quinine acts principally on the mature trophozoite stage of the parasite development and does not prevent sequestration or further development of circulating ring stages of P.Falciparum. Kills the sexual stages of P vivax,P ovale, P malariae but not mature gametocyes of P falciparum

24. Side effects? 1)Cinchonism -mild-- tinnitus,impaired hearing, headache, nausea, disturbed vision -severe-- vomiting, abd pain, diarrhea, severe vertigo 2) Hypersensitivity reactions - urticaria, bronchospasm, thrombocytopenia, hemolytic anemia to life threatening hemolytic uremic syndrome 3) ECG abnormalities -prolongation of QT interval

25. Side effects? IM injections –acidic and can cause pain, focal necrosis, abscess formation common cause of sciatic nerve injury. Rapid IV injection- hypotension and cardiac arrest Must be given only by infusion, never injection Overdose-oculotoxicity and cardiotoxicity

26. Treatment of P. vivax and P.ovale Infection Chloroquine 25 mg base/kg body weight divided over 3 days, combined with primaquine 0.25 mg base/kg body weight, taken with food once daily for 14 days is the treatment of choice for chloroquine-sensitive infections. in oceania and south-east asia, the dose of primaquine should be 0.5 mg/kg body weight. ACTs combined with primaquine for chloroquine-resistant vivax malaria.

27. Treatment of P. vivax and P.ovale Infection In mild-to-moderate G6pd deficiency , primaquine 0.75 mg base/kg body weight should be given once a week for 8 weeks. in severe G6pd deficiency, primaquine is contraindicated and should not be used. Where ACT (exception as+sp) has been adopted as the first-line treatment for P. falciparum malaria, it may also be used for P. vivax malaria in combination with primaquine for radical cure. artesunate plus sulfadoxine-pyrimethamine is not effective against P. vivax in many places.

28. World Malaria Day (previously Africa Malaria Day) 25 th April 2011