Chemotherapy of Malaria and National Drug Policy

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1 CHEMOTHERAPY,NATIONAL DRUG POLICY AND DRUG RESISTANCE IN MALARIA. DR .G . C. SAHU ROH&FW; GoI; AHMEDABAD Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Dr.G.C Sahu/ROHFW/GoI/A'Bad 2 SEQUENCE OF EVENTS… …. IN THE LIFE CYCLE OF MALARIA PARASITE Infective vector mosq.bite Sporozoite inoculation Liver cycle Repeatative RBC cycle Vec.mosq.picks up Gametocytes Mosquito cycle

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3 4 H U M A N M A L. P A R A S I T E S Dr.G.C Sahu/ROHFW/GoI/A'Bad

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4 An effective treatment policy should aim to: Reduce morbidity Prevent the progression of uncomplicated disease into severe and potentially fatal disease and thereby reduce malaria mortality Reduce the impact of placental malaria infection and maternal malaria-associated anaemia through chemoprophylaxis or preventive intermittent therapy. Prevent or delay the development of antimalarial drug resistance by correct diagnosis and rational treatment of all malaria positive cases. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Thus, in effect, a blood schizonticidal drug and primaquine should be administered to ALL types of malaria. Treatment of Malaria --- Aims Of Treatment 5 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Principles Of Treatment Treatment of malaria depends on the following factors: Type of infection. Severity of infection. Status of the host. Associated conditions/ diseases. 6 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Associated conditions/ diseases: Treatment of malaria may have to be modified due to certain associated conditions/ diseases. Therefore, all such should be carefully assessed before starting the patient on anti malarial treatment. Pregnancy: Treatment of malaria in pregnancy may prove to be difficult due to contra indication for use of certain antimalarials. Chloroquine can be used safely in all trimesters of pregnancy. Artemisinin is not shown to have any deleterious effects on the fetus in animal studies and therefore can be considered if the situation demands. Quinine can be used in pregnancy, but one should be watchful about hypoglycemia. Epilepsy: Malaria as well as anti malarials can trigger convulsions. Mefloquine is better avoided in these patients. Cardiac disease: High-grade fever of malaria can exacerbate left ventricular failure and therefore, in all such patients energetic management of malaria is called for. Fever should be controlled with anti-pyretics and tepid sponging. Chloroquine, artemisinin, pyrimethamine/ sulphadoxine, tetracyclines and primaquine can be safely used in these patients. Quinine can also be used carefully. Mefloquine and halofantrine are better avoided in patients with known cardiac illness. Hepatic insufficiency: None of the antimalarial drugs have any direct hepatotoxic effect. However, chloroquine is not advisable in patients with severe hepatic insufficiency. Renal failure: The initial dose of antimalarial drugs need not be reduced in patients with renal failure. However, if the patient requires parenteral antimalarials even after three days and continues to be sick, then the dose can be reduced by one third to half of usual dose. Dermatitis: Concomitant use of chloroquine with gold salts and phenyl butazone should be avoided because all the three can cause dermatitis. Anti-malarials contra-indicated in pregnancy. Mefloquine:- 1st trimester S-P combination:- 1st and last trimester Halo,Tetra,Doxy:- All trimester Primaquine:- All trimester. 7

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In an endemic area, malaria often presents with atypical manifestations Atypical features are more common in the following situations: Falciparum malaria Early infection Patients at extremes of age Patients who are immune-compromised (extremes of age, malnourished, AIDS, tuberculosis, cancers, on immunosuppressive therapy etc.) Patients on chemoprophylaxis for malaria Patients who have had recurrent attacks of malaria Patients with end stage organ failure Last but not the least, pregnancy. 8 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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9 INFORMATIONS ONE MUST HAVE BEFORE TREATING A CASE OF MALARIA. THE TYPE OF SPECIES YOU ARE TREATING i eP. VIVAX OR P. FALCIPARUM THE STAGE OF PARASITES YOU ARE TREATING i.e ASEXUAL STAGE(RING) OR SEXUAL STAGE(GAMETO) THE TYPE OF TREATEMENT YOU ARE GIVING i.e {PRESUMPTIVE TREATMENT OR RADICAL TREATMENT} Type of severity of infection i.e complicated or non complicated. THE TYPE OF AREA IN WHICH THE TREATMENT IS GIVEN i.e. LOW-RISK AREA OR HIGH RISK AREA. RESPONSE OF THE PARASITE TO THE DRUG GIVEN i.e. SENSITIVE OR RESISTANT. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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10 SCHIZONTICIDAL DRUGS: CHLOROQUINE, AMODIAQUINE, QUININE, QUINIDINE,PYREMETHAMINE, TRIMETHOPRIM, PROGUANIL, SULFONAMIDES IN COMBN. WITHPYREMETHAMINE, MEFLOQUINE, HALOFANTRINE, ARTEMESININE. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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11 GAMETOCIDAL AND ANTI-RELAPSE DRUG(S) : PRIMAQUINE Dr.G.C Sahu/ROHFW/GoI/A'Bad

What would be the optimal anti-malaria compound?(1) : 

What would be the optimal anti-malaria compound?(1) The optimal anti-malaria compound must have such six advantages therapeutically as follows: High efficacy The 28-day cure rate should be over 95% in multi-drugs resistant falciparum malaria endemic areas Quick acting The development of parasites should be stopped after the initial dose, which is the key point to reduce the incidence of cerebral malaria , thereby, reduced the mortality of malaria 12 Dr.G.C Sahu/ROHFW/GoI/A'Bad

What would be the optimal anti-malaria compound?(2) : 

What would be the optimal anti-malaria compound?(2) Short treatment course The optimal treatment course with better patients' compliance would be once daily for just two days. Low toxicity The incidence of side effects should be less than 5%. 13 Dr.G.C Sahu/ROHFW/GoI/A'Bad

What would be the optimal anti-malaria compound?(3) : 

What would be the optimal anti-malaria compound?(3) Preventing transmission It will be advantages to control the prevalence of malaria and very important for preventing from the disease to neutralize and kill quickly the gametocytes of falciparum malaria Low cost It should be affordable for most of the patients in malaria endemic areas of the developing countries, so that those patients could take the drug to cure malaria. 14 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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15 15 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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16 Anti Malarial Drugs: Chloroquine Mechanism of action: The mechanism of action of chloroquine is unclear. Being alkaline, the drug reaches high concentration within the food vacuoles of the parasite and raises its pH. It is found to induce rapid clumping of the pigment. Chloroquine inhibits the parasitic enzyme heme polymerase that converts the toxic heme into non-toxic hemazoin, thereby resulting in the accumulation of toxic heme within the parasite. It may also interfere with the biosynthesis of nucleic acids. Other mechanisms suggested include formation of drug-heme complex, intercalation of the drug with the parasitic DNA etc. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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17 Anti Malarial Drugs: Quinine Mechanism of action: Quinine acts as a blood schizonticide although it also has gametocytocidal activity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is said to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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18 Pyrimethamine and sulphadoxine are very useful adjuncts in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria. Anti malarial activity: Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are so essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver. Availability: Pyrimethamine and sulphadoxine combined tablets are available, containing 25 mg of pyrimethamine and 500 mg of sulphadoxine in each tablet. Dose of Pyrimethamine/sulfadoxine: 3 tablets as per the WHO recommendations Anti Malarial Drugs: Pyrimethamine/ Sulphadoxine Dr.G.C Sahu/ROHFW/GoI/A'Bad

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19 Anti Malarial Drugs:Mefloquine Mefloquine was born during the Vietnam war, as a result of research into newer anti malarials, to protect the American soldiers from the multi drug resistant falciparum malaria. Nothing much has happened after that and hence this 'new' drug should be restricted for use against multi drug resistant falciparum only. Anti malarial activity: Mefloquine has been found to produce swelling of the P. falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components. It is effective against the blood forms of falciparum malaria, including the chloroquine resistant types. Availability: It is available as 250 mg tablets. Dose: 15 mg/kg in a single dose. If the dose exceeds 1000 mg, the second dose can be given after 4-8 hours to minimise gastric irritation. Total dose should not exceed 1500 mg. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Artemesia annua Sweet Annie Sweet wormwood Annual wormwood Qinghao 20 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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21 Anti Malarial Drugs: It is the fastest acting anti malarial available. It inhibits the development of the trophozoites and thus prevents progression of the disease. It starts acting within 12 hours. It is also effective against the chloroquine resistant strains of P. falciparum. These properties of the drug are very useful in managing complicated P. falciparum malaria. Dose: Artemether: 3.2 mg/kg intra muscularly as a loading dose, followed by 1.6 mg/kg daily until oral therapy or a maximum of 7 days. Arteether: 3 mg/kg once a day for 3 days, as deep intra muscular injection. Artesunate: Oral- 5 mg/kg on the first day followed by 2.5 mg/kg on the second and third days. Oral artesunate is not recommended in pregnancy. Parenteral- Loading dose of 2.4 mg/kg followed by 1mg/kg after 4 hours and 24 hours; thereafter, 1.2 mg/kg daily for maximum of 7 days. For children, the recommended dose is 1.2 mg/kg/day for 5-7 days. Anti Malarial Drugs: The Artemisinin Derivatives Dr.G.C Sahu/ROHFW/GoI/A'Bad

Site of Action : 

Site of Action Artemisinin Artemisinin Conventional Treatment 22 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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23 Anti Malaria Drugs: Primaquine Primaquine is the essential co-drug with chloroquine in treating all cases of malaria. It is highly effective against the gametocytes of all plasmodia and thereby prevents spread of the disease to the mosquito from the patient. It is also effective against the dormant tissue forms of P. vivax and P. ovale malaria, and thereby offers radical cure and prevents relapses. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent. Mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite. Availability: Primaquine is available as tablets containing 2.5, 7.5 and 15 mg of the salt. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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24 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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25 What is presumptive treatment? ** Presumption - In an area with high transmission of malaria, it should be presumed that ALL cases of fever are due to malaria. Treatment - First loading dose of chloroquine should be administered immediately after collecting the blood specimen, even without waiting for its report. If the fever is indeed malaria, this treatment alleviates symptoms early, may be well before the test result is available. If it is malaria, chloroquine also prevents the spread of malaria by destroying the gametocytes of P. vivax (the more common malaria). If it is not malaria, nothing is lost, for chloroquine at this dose is safe and has no adverse effects. It cures early and more important, it prevents spread of P. vivax malaria. ** Till recently , it was recommended treatment under the National Malaria Eradication Programme(now NVBDCP) in India. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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THE NATIONAL ANTI MALARIA DRUG POLICY-2010 “APPROPRIATE FOR TODAY AND SAFE FOR TOMORROW” 26 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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27 THE NATIONAL ANTI MALARIA DRUG POLICY-2010 “APPROPRIATE FOR TODAY AND SAFE FOR TOMORROW”  Providing complete cure (clinical and parasitological) of malaria cases  Prevention of progression of uncomplicated malaria into severe malaria and thereby reduce malaria mortality  Prevention of relapses by administration of radical treatment  Interruption of transmission of malaria by use of gametocytocidal drugs  Preventing development of drug resistance by rational treatment of malaria cases. Effective treatment of malaria under the National Drug Policy aims at: Dr.G.C Sahu/ROHFW/GoI/A'Bad

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28 All fever cases suspected to be malaria should be investigated by microscopy or RDT. 1. P.vivax cases should be treated with chloroquine for three days and Primaquine for 14 days. Primaquine is used to prevent relapse but is contraindicated in pregnant women, infants and individuals with G6PD deficiency. Note: Patients should be instructed to report back in case of haematuria or high colored urine /cyanosis or blue coloration of lips and Primaquine should be stopped in such cases. Care should be taken in patients with anaemia. 2. P. falciparum cases should be treated with ACT (Artesunate 3 days + Sulphadoxine-Pyrimethamine 1 day). This is to be accompanied by single dose primaquine preferably on day 2. 3. Pregnant women with uncomplicated P. falciparum should be treated as follows:  1st Trimester: Quinine  2nd & 3rd Trimester: ACT Note: Primaquine is contra indicated in pregnant woman Treatment of uncomplicated malaria Dr.G.C Sahu/ROHFW/GoI/A'Bad

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29 5. In cases where parasitological diagnosis is not possible due to non-availability of either timely microscopy or RDT, suspected malaria cases will be treated with full course of chloroquine, till the results of microscopy are received. Once the parasitological diagnosis is available, appropriate treatment as per the species, is to be administered. 6. Presumptive treatment with chloroquine is no more recommended. 7. Resistance should be suspected if in spite of full treatment with no history of vomiting, diarrhoea, patient does not respond within 72 hours, clinically and parasitologically. Such cases not responding to ACT, should be treated with oral quinine with Tetracycline / Doxycycline. These instances should be reported to concerned District Malaria /State Malaria Officer/ROHFW for initiation of therapeutic efficacy studies. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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30 1. Chloroquine: 25 mg/kg body weight divided over three days i.e. 10mg/kg on day 1, 10mg/kg on day 2 and 5mg/kg on day 3. 2. Primaquine: 0.25 mg/kg body weight daily for 14 days. DRUG SCHEDULE FOR TREATMENT OF MALARIA UNDER NVBDCP * Primaquine is contraindicated in infants, pregnant women and individuals with G6PD deficiency. 14 day regimen of Primaquine should be given under supervision. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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31 Artemisinin based Combination Therapy (ACT)*  Artesunate 4 mg/kg body weight daily for 3 days Plus  Sulfadoxine (25 mg/kg body weight) . Pyrimethamine (1.25 mg/kg body weight) on first day. * ACT is not to be given in 1st trimester of pregnancy. Treatment of uncomplicated P.falciparum cases Dr.G.C Sahu/ROHFW/GoI/A'Bad

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32 Treatment of uncomplicated P.falciparum cases in pregnancy 1st Trimester : Quinine salt 10mg/kg 3 times daily for 7 days. Note: Quinine may induce hypoglycemia; pregnant women should not start taking quinine on an empty stomach and should eat regularly, while on quinine treatment. 2nd and 3rd trimester: ACT as per dosage given above. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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33 Treatment of mixed infections (P.vivax + P.falciparum) cases All mixed infections should be treated with full course of ACT and Primaquine 0.25 mg per kg body weight daily for 14 days. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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34 Treatment of severe malaria cases: Severe malaria is an emergency and treatment should be given as per severity and associated complications which can best be decided by the treating physician. The guidelines for specific antimalarial therapy is as follows: Artesunate: 2.4 mg/kg body weight IV or IM given on admission (time = 0 h); then at 12 h and 24 h and then once a day. (or)  Artemether: 3.2 mg/kg body weight IM given on admission and then 1.6 mg/kg body weight per day. (or)  Arteether: 150 mg IM daily for 3 days in adults only (not recommended for children). (or)  Quinine: 20 mg/kg* body weight on admission (IV infusion or divided IM injection) followed by maintenance dose of 10 mg/kg body weight 8 hourly. The infusion rate should not exceed 5 mg salt/kg body weight per hour. (*loading dose of Quinine i.e. 20mg /kg body weight on admission may not be given if the patient has already received quinine or if the clinician feels inappropriate). Note:The parenteral treatment in severe malaria cases should be given for minimum of 24 hours once started (irrespective of the patient.s ability to tolerate oral medication earlier than 24 hours). 34

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35 1.. After parenteral artemisinin therapy, patients will receive a full course of oral ACT for 3 days. 2.. Those patients who received parenteral Quinine therapy should receive: Oral Quinine 10 mg/kg body weight three times a day for 7 days (including the days when parenteral Quinine was administered) plus Doxycycline 3 mg/kg body weight once a day or Clindamycin 10 mg/kg body weight 12-hourly for 7 days (Doxycycline is contraindicated in pregnant women and children under 8 years of age). 35 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Why injectable Arteether Over injectable Artesunate & injectable Artemether in the National Drug Policy ??? Immediate onset and rapid reduction of parasitaemia with complete clearance in most cases within 48 hours Clinical recovery of the patient, e.g. defervescence is faster than with other antimalarials. Therapeutically equivalent to quinine in cerebral malaria More lipophilic properties than artemether favouring accumulation in brain tissue and thus the treatment of cerebral malaria were regarded as advantages over the other compounds. Arteether has much slower elimination.[elimination half life:Arteether-20 hrs;Artemether-6hrs;Artesunate-1hr] Inj.ARTEETHER: 36 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Artemisinins 37 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Comparative Efficacy : In Cerebral Malaria 38 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Important for Rx Most blood schizonticidal drugs prevent the development of the forthcoming erythrocytic cycle of parasitic development and hence have no or little effect on the ongoing cycle that is already causing fever. Therefore, it would take at least 48 hours for the treatment to be effective. In severe P. falciparum malaria, oral antimalarials should not be used. Vomiting, poor general health, poor compliance, erratic G.I. absorption due to splanchnic vasculopathy etc. make oral therapy less reliable. Therefore, use only parenteral antimalarials. This also means that oral only antimalarials like Mefloquine and Halofantrine have no place in treating severe falciparum malaria. In all cases of P. falciparum malaria, the antimalarial drugs should be chosen depending on the severity of the illness and the sensitivity pattern in the locality. Changing the drugs or adding the drugs in between is not advisable. 39 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Most antimalarial drugs have a long plasma half-life. Therefore, adding similar drugs half way through the treatment will only add to the adverse effects and not to the therapeutic benefit. The following combinations should therefore be avoided, concurrently or within a short interval: Do not exceed the maximum recommended dose of antimalarial drugs. All antimalarial drugs have a narrow safety range and excess dose may lead to adverse effects. Moreover, larger dose does not offer any superior antimalarial effect. …..Important for Rx Chloroquine + Quinine Chloroquine + Mefloquine Quinine + Mefloquine Quinine + Primaquine Quinine + Halofantrine Mefloquine + Primaquine Administration of Primaquine and Pyrimethamine/sulphadoxine on the same day is also not advisable. Both sulpha and primaquine can precipitate hemolytic crisis in patients with Glucose 6-phosphate dehydrogenase deficiency. 40 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Primaquine should be administered to ALL cases of malaria as radical treatment except in the following situations where it is contraindicated: Do not misuse the newer antimalarial drugs. We need to preserve them for future. ……..Important for Rx Pregnancy and lactation Infants below one year of age. In these two categories, chloroquine should be given every week as a suppressive chemoprophylaxis to prevent relapse of vivax malaria. When these patients are fit for administration of primaquine, they should be given full therapeutic dose of chloroquine as well as primaquine. Patients with known Glucose 6-phosphate dehydrogenase deficiency Concurrently with quinine, mefloquine and halofantrine It should not be used on the same day with sulphadoxine. In such cases it can be given the next day. Research into newer antimalarial drugs is scanty and the parasite is fast developing resistance even for newer drugs. Thus if we deplete the newer drugs by misusing them, we may not have anything left for treating ALL DRUG RESISTANT malaria in the not-too-far-future. Therefore, newer anti malarial drugs should be used only when definitely indicated and not indiscriminately. These drugs should be used ONLY when parasite index or other methods PROVE drug resistant malaria. In addition, artemisinin derivatives can be used in cases of hyperparasitemia or life-threatening complications on account of their ability to clear the parasitemia earlier compared to other anti malarial drugs. Dr.G.C Sahu/ROHFW/GoI/A'Bad 41

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While most of the the clinical manifestations of malaria are caused by the malarial infection per se……………… High grade fever as well as the side effects of anti malarial therapy can also contribute to the clinical manifestations. All these may act in unison, further confusing the picture. In some cases, secondary infections like pneumonia or urinary tract infection can add to the woes. All the above facts should always be kept in mind. 42 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Artemisinin based combinations are known to improve cure rates, reduce the development of resistance and they might decrease transmission of drug-resistant parasites. The total effect of artemisinin combinations (which can be simultaneous or sequential) is to reduce the chance of parasite recrudescence, reduce the within-patient selection pressure, and prevent transmission. Artemisinin based combinations- 1 Artesunate + Chloroquine 43 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Artemisinin based combinations - 2 Artesunate + Sulfadoxine/Pyrimethamine (SP) 44 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Artemisinin based combinations - 3 Artemether + Lumefantrine (Coartem,TM RiametTM) 45 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Combination therapies recommended by WHO 46 Dr.G.C Sahu/ROHFW/GoI/A'Bad

How and when can Artemisinin drugs be affordable for most malaria patients in the world? : 

How and when can Artemisinin drugs be affordable for most malaria patients in the world? 47 Dr.G.C Sahu/ROHFW/GoI/A'Bad

Using compounds to replace the single-ingredient drugs should be recommended. : 

Using compounds to replace the single-ingredient drugs should be recommended. Artemisinin drugs Alone： High consuming of Artemisinin High cost Long treatment course Artemisinin compounds(ACT)： Low consuming of artemisinin Lower cost Short treatment course Low recrudescence, easy to finish the complete treatment course. 48 Dr.G.C Sahu/ROHFW/GoI/A'Bad

Parasitological rationale for combination treatment : 

Parasitological rationale for combination treatment If for example 1 of 106 parasites is resistant to treatment A and 1 of 106 parasites is resistant to treatment B, then 1 of 1012 will be resistant to both. A typical malaria patient would have 1010 parasites 49 Dr.G.C Sahu/ROHFW/GoI/A'Bad

Practical rationale for combination therapy : 

Practical rationale for combination therapy Most of the artemisinin drug combination regimens last 3 days and are well tolerated Hence high compliance High compliance + high efficacy = high effectiveness High effectiveness means long durability Long durability means rarer policy changes with their inevitable costs and woes 50 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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51 Quick comparison between blood schizonticidal drugs 51 Dr.G.C Sahu/ROHFW/GoI/A'Bad

Malaria Parasite Resistance : 

Malaria Parasite Resistance Mechanism of resistance is due to genetic mutations in malaria parasite Resistance Delayed Response Recurrence of Infection Increased Gametocyte Increase Transmission Increased Clinical Cases More Drug Used 52 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Dr.G.C Sahu/ROHFW/GoI/A'Bad 53 The Acts of Commissions And Omissions IN MALARIA. 53 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Dr.G.C Sahu/ROHFW/GoI/A'Bad 54 54 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Dr.G.C Sahu/ROHFW/GoI/A'Bad 55 55 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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Dr.G.C Sahu/ROHFW/GoI/A'Bad 56 Examination of blood smear Demonstration of the parasite in a smear of the blood definitely establishes the presence of malaria. A negative finding on examination does not rule out malaria. Only 50% of children with malaria are smear positive, even on repeated examination. A positive finding on examination does not confirm clinical malaria, especially in patients from an endemic area, in whom a symptomatic parasitemia often exists. Both thick and thin films are essential. If the parasitemia is light, a thin film examination may miss the diagnosis. Thick films save time in diagnosis of scanty infections but make species identification of the parasite difficult. At least 100-200 fields of a thick film should be scrutinized before a slide is reported as negative for malaria. In doubtful cases, the examination can be repeated after 4 hours. Various techniques to enhance the diagnostic utility of the peripheral blood smear examination are in use. Fluorescent staining and microscopy, centrifugation, selective magnetic separation techniques, and other techniques have been used but have only a moderate effect. 56 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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57 Treatment of P. vivax malaria: A flow chart Chloroquine + Primaquine After 48 hours Clinical Recovery Status quo / worse Continue the treatmentRepeat the M.P. test on the 6th day Suspect P. falciparum, repeat M.P. test at 48 hrs. (A thin smear examination is better for species identification and for assessing parasite count) NEGATIVE POSITIVE Cured POSITIVE NEGATIVE Consider other causes of fever, may be in association with malaria P. Falciparum Treat as possibly chloroquine resistant P. Vivax If the patient has typical malarial complications, treat as P. falciparum; otherwise, wait. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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58 Treatment of P. falciparum malaria -A flow chart Dr.G.C Sahu/ROHFW/GoI/A'Bad

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59 Drugs for chloroquine resistant Pf malaria Dr.G.C Sahu/ROHFW/GoI/A'Bad

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60 Clinical approach to cases of recurrent malaria Dr.G.C Sahu/ROHFW/GoI/A'Bad

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61 Established anti-malarial drugs Dr.G.C Sahu/ROHFW/GoI/A'Bad

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62 New Anti-malarial drugs Dr.G.C Sahu/ROHFW/GoI/A'Bad

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63 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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64 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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65 1 tablet consists of 26.3 mg pimaquine phosphate, 15 mg primaquine base. …..So there is no absolute contraindication ! ! Dr.G.C Sahu/ROHFW/GoI/A'Bad

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66 Malaria is a preventable infection that can be fatal if left untreated. Currently, you cannot be vaccinated against malaria, but you can protect yourself Dr.G.C Sahu/ROHFW/GoI/A'Bad

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67 Characteristics of thick and thin blood smears Dr.G.C Sahu/ROHFW/GoI/A'Bad

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68 Level of parasitemia and clinical correlates Dr.G.C Sahu/ROHFW/GoI/A'Bad

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69 MALARIA--- THINK BEYOND CLINICAL CURE  SOME POINTS TO PONDER FOR PHYSICIANS  Ø CLINICAL CURE WITH APPROPRIATE BLOOD SCHIZONTICIDALS Ø GAMETOCYTES,WHEN LATER SUCKED BY THE VECTOR MOSQUITOS,DEVELOP IN THEIR BODY INTO DISEASE CAUSING SPOROZOITES WHICH ARE TRANSMITTED AGAIN TO THE NEXT HEALTHY PERSON BY THE MOSQUITO BITE –THUS ANOTHER HUMAN BEING FALLS VICTIM TO THE DEADLY MALARIA .  Ø THIS TRANSMISSION OF MALARIA CAN BE PREVENTED BY ADMINISTERING GAMETOCYTOIDAL DRUGS LIKE PRIMAQUINE AFTER CONTROLLING THE ACUTE STAGES OF THE DISEASE . Ø THE PRACTICE OF USING GAMETOCYTOCIDAL DRUGS SHOULD BE CONSIDERED AS IMPORTANT AND SHOULD BECOME A PART OF STANDARD TREATEMENT STRATEGY WHENEVER A CASE OF P.FALCIPARUM IS ENCOUNTERED. ……contd 69 Dr.G.C Sahu/ROHFW/GoI/A'Bad

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70 Control of malaria is a complex chain of measures that often complement one another. The above diagram depicts this control chain: For example, by taking personal protective measures, three things can be achieved - prevention of malaria in the given individual, thus reduced parasite load and reduction in spread, and by denying blood meal to the mosquito the egg laying is also hampered! In the recent years, more emphasis is being laid on early diagnosis and treatment, on personal protection especially with insecticide treated bednets and on biological vector control. By these means, it is intended to minimise use of potentially harmful chemical insecticides. Dr.G.C Sahu/ROHFW/GoI/A'Bad

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71 Fight The Bite......... Before it is too late......... Dr.G.C Sahu/ROHFW/GoI/A'Bad