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    Management of Malaria in Indian Context


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    1 : MANAGEMENT OF MALARIA Speaker : Dr. Sujit Kr. Kundu. MD(PGT). Dept. of Pediatrics N.B.M.C & H. Darjeeling, India.
    3 : Clinical picture of Uncomplicated Malaria Symptoms: fever, chills, headache, body pains, diarrhea, vomiting, cough Signs: anemia, thrombocytopenia Symptoms may be very nonspecific Synchronous infections with predictable cycles of symptoms are rare
    4 : Features of severe malaria Decrease in conscious level, focal neurological signs or multiple convulsions. Metabolic acidosis - Kussmaul’s breathing. Severe anemia – Hematocrit < 15 % Hyperpyrexia Hyperparasitemia > 5 % Hypoglycemia (glucose < 2.2 mmol/L) Renal impairment or oliguria Pulmonary edema, hypoxia, Circulatory collapse or shock Hemostasis abnormalities – hemolysis, DIC. Jaundice – rare in children.
    6 : DIAGNOSIS - Laboratory Peripheral Smear : Quantitative Buffy Coat (QBC) test : Rapid diagnostic test : Polymerase chain reaction : Other investigation.
    7 : DIAGNOSIS- PS PERIPHERAL SMEAR : Gold standard Thick smear : for Screening of parasites , infected RBC counted against WBC – 200 WBC/100 fields. Sensitivity 5-10 parasite/mcl.. Thin smear : for identifying Species. S – 200 p /mcl. Infected RBC /1000 RBC converted into %.
    8 : Differentiation of falciparum Ring forms PF trophozoite Large ring PV trophozoite
    9 : Differentiation of falciparum P.falciparum schizonts P.vivax schizonts
    10 : Differentiation of falciparum P.falciparum gametocyte P.vivax gametocyte
    11 : Falciparum gametocytes Male Female
    12 : Electron Micrographs P.falciparum EM P.vivax EM
    13 : Falciparum invading RBC
    14 : DIAGNOSIS -QBC TEST staining of centrifuged & compressed Red cell layer in a specialized capillary tubes in which parasite DNA is stained with acridine orange. 60 mcl of blood from finger, ear or heel sufficient. Fluorescing parasite observed at the RBC WBC interface. Detected by UV light source. More Sensitive than traditional Thick smaer preparation. Negative reported in 1 mins, positive in few mins.
    15 : DIAGNOSIS- RDT Detects malaria Ag – PfHPR2/PMA/pLDH OptiMAL test – utilise LDH, distinguish Fal with Non fal. Detection limit 100-200 pf/mcl. Positive test means viable parasite. PfHRP2 – detect only PF as this soluble pr. only expressed on RBC mem. infected by PF. 40-100 pf/mcl . PMA – Pan specific Plasmodium Aldolase. Detect any of the 4 species. Differentiation possible PF & Non pf.
    16 : RDT
    17 :
    18 : DIAGNOSIS- PCR 10 TIMES MORE sensitive than microscopy. More specific also. Epidemiological tool. Can detect Ab by IF or EIA. Intraleukocytic malarial pigment suggested as a measure of Ds severity. Flowcytometry DNA fluorescence.
    20 : Immediate management : Coma scoring Exclude other causes of coma 1. ABC of coma care 2. correct hypoglycemia & electrolytes. 3. Correct dehydration 2. Prompt institution of antimalarials 3. Treatment of hyperpyrexia 4. Management of other complications 5. Treatment of associated infections 17
    21 : Investigation to detect Complications Blood : parasite count, sugar, CBC, Platelet count, Grouping & CM, ABG analysis, Electrolytes, Urea , Creatinine, Culture, Coagulation profile, Liver enzymes. CSF Urine Chest X-ray
    22 : ANTIMALARIAL THERAPY Chloroquine Quinine Quinidine Artemisinin derivatives Others
    23 : Quinine 1st line in majority of the world. Can be given by iv /im/oral routes. Acts on mature trophozoite stage only. Can cause hypoglycemia , Cinchonism,
    24 : Quinidine D- isomer of quinine. More effective than quinine but more Cardiotoxic, Hypotension, QTc prolongation. Rarely used in India.
    25 : Artemisinin derivatives Convenient dosing, acts on all stages of parasites, faster acting, less side effect profile, But till date NO difference in efficacy & safety in comparison with quinine. Allergic reaction, reticulocyte count may drop transiently, ? Neurotoxicity. Use with other AM to prevent resistance.
    26 : Falciparum malaria is now resistant to most drugs except artemesin based derivatives and more than 80 countries have now adopted artemesin based combination therapy (ACT) as first line drug. These drugs are expensive and should be used after confirmation of diagnosis. After the distressing news of emergence of artemesin resistance at the Thai-Cambodia border, alarm bells have started ringing. WHO recommends oral artemisinin-based monotherapy should be removed from the market because their use will hasten the development of parasite resistance. Indian Pediatr July 2010;47: 369
    27 : There has been a recent increase in the number of RCT’s in malaria and the current guidelines are strongly evidence based. The following ACTs are currently recommended by the WHO for falciparum malaria: 1. artemether+ lumefantrine, 2. artesunate + amodiaquine, 3. artesunate + mefloquine, 4. artesunate + sulfadoxine–pyrimethamine. WHO has now added a fifth ACT – 5. dihydroartemisinin plus piperaquine - to the previous list of recommended medicines Indian Pediatr July 2010;47: 369
    28 : Other antimalarials Halofantrine, Mefloquine, Atavaquone, Sulfa-Pyrm, Doxycycline, Tetracycline, . To reduce the period of parenteral tx. Improve compliance, Prevent resistance.
    29 : Exo- erythrocytic (hepatic) cycle Malaria Life Cycle
    30 : Malaria Transmission Cycle Parasite undergoes sexual reproduction in the mosquito Some merozoites differentiate into male or female gametocyctes Erythrocytic Cycle: Merozoites infect red blood cells to form schizonts Dormant liver stages (hypnozoites) of P. vivax and P. ovale Exo-erythrocytic (hepatic) Cycle: Sporozoites infect liver cells and develop into schizonts, which release merozoites into the blood MOSQUITO HUMAN Sporozoites injected into human host during blood meal Parasites mature in mosquito midgut and migrate to salivary glands
    31 : The Malaria Transmission Cycle Sites of Action for Antimalarial Drugs SPORONTOCIDES: primaquine pyrimethamine proguanil MOSQUITO HUMAN GAMETOCYTOCIDES: primaquine TISSUE SCHIZONTOCIDES: primaquine pyrimethamine proguanil tetracyclines BLOOD SCHIZONTOCIDES: chloroquine mefloquine quinine/quinidine tetracyclines halofantrine sulfadoxine pyrimethamine artemisinins
    32 : Supportive Therapy Antibiotics Anticonvulsants Blood transfusion & Exchange transfusion Dialysis IVF Dopamine Correction of hypoglycemia Mannitol for raised ICP Mechanical Ventilation
    33 : NATIONAL DRUG POLICY ON MALARIA (2010) Preamble Malaria is one of the major public health problems of the country. Around 1.5 million laboratory confirmed cases of malaria are annually reported in India. Around 50% of the total malaria cases reported is due to P.falciparum. One of the reasons attributed to rise in proportion of P.falciparum cases is resistance to chloroquine, which was used for a long time as the first line of treatment of malaria cases. P.falciparum infections are known to lead to severe malaria, if timely treatment with effective drugsis not administered. The National Drug Policy on Malaria was first formulated in 1982 and has subsequently been reviewed and revised periodically. The present National Drug Policy for Malaria (2010) has been drafted keeping in view the availability of moreeffective antimalarial drugs and drug resistance status in the country.
    34 : Early diagnosis and complete treatment is one of the key strategies of the National Malaria Control Programme. All fever cases clinically suspected of malaria should be investigated for confirmation of malaria by either microscopy or Rapid Diagnostic Test (RDT)1. In high Pf predominant areas where it is not possible to get microscopy results within24 hours, ASHAs/other community health volunteers/MPWs should be provided with rapid diagnostic kits and anti-malarials (including ACT) for early diagnosis and treatment of P.falciparum cases. Effective treatment of malaria under the National Drug Policy aims at: ? 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. 1
    35 : Treatment of uncomplicated malaria 1. All fever cases suspected to be malaria should be investigated by microscopy or RDT. 2. P.vivax cases should be treated with chloroquine for three days and Primaquinefor 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 shouldbe taken in patients with anaemia. 3. P. falciparum cases should be treated with ACT (Artesunate 3 days + Sulphadoxine-Pyrimethamine 1 day). This is to be accompanied by single dose primaquine on day 2. 4. 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
    36 : 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.
    37 : DRUG SCHEDULE FOR TREATMENT OF MALARIA UNDER NVBDCP Treatment of P.vivax cases 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. Primaquine is contraindicated in infants, pregnant women and individuals with G6PD deficiency. 14day regimen of Primaquine should be given under supervision.
    38 : Treatment of uncomplicated P.falciparum cases 1. 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
    39 : 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.
    40 : 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. 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:
    41 : ? 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 oncestarted (irrespective of the patient.s ability to tolerate oral medication earlier than 24 hours).
    42 : After parenteral artemisinin therapy, patients will receive a full course of oral ACT for 3 days. 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/kgbody weight once a day or Clindamycin 10 mg/kg body weight 12-hourly for 7days (Doxycycline is contraindicated in pregnant women and children under 8years of age). (or) ? ACT as described
    43 : Chemoprophylaxis Chemoprophylaxis should be administered only in selective groups in high P.falciparum endemic areas. Use of personal protection measures including Insecticide Treated bed Nets (ITN) / Long Lasting Insecticidal Nets (LLIN) should be encouraged for pregnant women and other vulnerable population including travellers for longer stay. However, for longer stay of Military and Para-military forces in high Pf endemic areas, the practice of chemoprophylaxis should be followed wherever appropriate e.g. troops on night patrol duty and decisions of their Medical Administrative Authority should be followed.
    44 : Short term chemoprophylaxis (up to 6 weeks) Doxycycline: 100 mg once daily for adults and 1.5 mg/kg once daily for children (contraindicated in children below 8 years). The drug should be started 2 days before travel and continued for 4 weeks after leaving the malarious area. Note: It is not recommended for pregnant women and children less than 8 years. Chemoprophylaxis for longer stay (more than 6 weeks) Mefloquine: 250 mg weekly for adults and should be administered two weeks before, during and four weeks after exposure. Note: Mefloquine is contraindicated in individuals with history of convulsions, neuropsychiatric problems and cardiac conditions. Therefore, necessary precautions should be taken and all should undergo screening before prescription of the drug.
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