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Current update in treatment of Malaria Prof. K.M. Bhatt,EBS UON PRINCIPLES OF MANAGEMENT OF UNCOMPLICATED MALARIA Prompt and accurate diagnosis Assess for signs of complicated/severe malaria Can occur with low parasitemias Can develop after parasites clear peripherally Prompt use of appropriate antimalarial drugs Monitor clinical and parasitological improvement Cure – parasitic and/or clinical Ancillary treatment Instructions for future prevention of malaria OBJECTIVES OF AN EFFICIENT ANTIMALARIAL TREATMENT Allow for a lasting clinical recovery Reduce malaria-related morbidity and mortality Stop the evolution of a benign infecton into a serious and potentially life-threatening disease Reduce the impact of malaria-related placenta infection and malaria-related maternal anemia using chemoprophylaxis or intermittent preventive treatment Minimize the risks and levels of resistance. Characteristics of ideal antimalarial combination The elimination half life of the partner drug is longer than that of the fast-acting drug. The tolerability must be good and the toxicity acceptable The treatment must be active against all stages of the parasite, including gametocytes (Drugs, 2002, Vol. 62, No. 9, p. 1315-1329) Characteristics of ideal antimalarial combination The total duration of the regimen must not exceed 3 days to ensure adequate adherence One of the drugs must be present in the circulation after the 2 cycles exposed to the fast acting drug (Drugs, 2002,62(9):1315-1329) Recommended ACTs For Uncomplicated Falciparum Malaria Artemether-lumefantrine Artesunate + amodiaquine -Significant resistance to Amodiaquine in Kenya* Artesunate + mefloquine Artesunate + SP – obsolete in Kenya* Dihydroartemisinin + piperaquine Drug Resistance Drug resistance to nearly all the drugs in current use … Severe Malaria Clinical and Laboratory Investigations Detailed clinical examination Asses level of consciousness and record Glasgow or Blantyre coma scale Blood glucose HB, platelet count Blood slide for MPs Liver, renal function tests Clotting studies Blood cultures Blood pH and gases Chest x-ray Blood cross matching LP (after fundoscopy) Weight BACTERIAL INFECTION Patients with severe malaria are vulnerable to bacterial infection. Much more common in children. Severe malaria predisposes to bacteremia, often enteric bacteria from the gut (site of preferential parasitized erythrocyte sequestration). Predisposes to systemic non-typhoid salmonella infections Prevalence of Anaemia In Children More than half of children under 5 years had moderate to severe anaemia. Anaemia more common in younger children. Anaemia prevalence ranging from 16% in low endemicity areas to 34% in lake region. Treatment of Severe and Complicated Malaria parenteral Artesunate at 2.4mg per Kg stat iv and repeated after 12 hr, 24hr and then for 6 days daily Parenteral quinine (to be phased out soon) Loading dose 20mg/kg thereafter 10mg/kg 8 hrly (as infusion in 5% dextrose to run over 4 hrs Change to oral ACT as soon as the patient can tolerate oral medication preferably 24hrs. Treatment of Severe and Complicated Malaria parenteral Artesunate at 2.4mg per Kg stat iv and repeated after 12 hr, 24hr and then for 6 days daily Parenteral quinine Loading dose 20mg/kg thereafter 10mg/kg 8 hrly (as infusion in 5% dextrose to run over 4 hrs) Change to oral ACT as soon as the patient can tolerate oral medication preferably 24hrs. Supportive Care Coma – maintain airway, intubate Hyperpyrexia – tepid sponging, antipyretic drugs Convulsions – maintain airway, IV or rectal diazepam or IM paraldehyde Hypoglycaemia – maintain glucose containing infusion Severe anaemia – transfuse fresh whole blood Acute pulmonary oedema – prop up patient at 45 degrees, give oxygen, give diuretics, stop IV fluids, +ve pressure respirator Cont… Acute renal failure – dialysis Bleeding and coagulopathy – transfuse frozen plasma, vitamin K injection Exchange transfusion for hyperparasitaemia In children severe respiratory distress results from severe metabolic acidosis and anaemia. Should be treated by blood transfusion Manitol for raised intracranial pressure EXCHANGE TRANSFUSION CDC recommends that exchange transfusion be strongly considered for persons with a parasite density of more than 10% or if complications such as cerebral malaria, non-volume overload pulmonary edema, or renal complications exist. Its beneficial effect by removing infected red cells, improving the rheological properties of blood, and reducing toxic factors such as parasite derived toxins, harmful metabolites, and cytokines. ERYTHROCYTAPHARESIS Red blood cell fraction is removed by apheresis and wherein the plasma, leukocyte and platelet fractions are returned to the patient [2] Erythrocytapheresis has advantages over ET because of speed, efficiency, haemodynamic stability and retention of plasma components such as clotting factors, but would only be available in specialized centres and lacks the advantage of ET of removing and replacing plasma 2. Zhang Y, Telleria L, Vinetz JM et al. Erythrocytapheresis for Plasmodium falciparum infection complicated by cerebral malaria and hyperparasitemia. J Clin Apheresis 2001;16:15–18. WHO 2012 RECOMMENDS: A single dose 0.25mg base/Kg Primaquine dose should be given to all patients with parasitologically confirmed P.falciparum malaria on the 1st day of treatment in addition to an ACT, except for pregnant women and <1yr of age Add quinine IV to AS IV in case of non-responding parasitaemia in severe malaria Treatment In Specific Populations And Situations Malaria in pregnancy Malaria in lactating women HIV and Malaria ARVs and antimalarials Treatment In Specific Populations And Situations Pregnant Women: Recommendations –obtain parasitological diagnisis • First trimester: quinine + clindamycin to be given for 7 days. • ACT should be used if it is the only effective treatment available. • Second and third trimesters: ACT known to be effective in the country/region or artesunate + clindamycin to be given for 7 days or quinine + clindamycin to be given for 7 days. WHO guidelines 2010 Malaria in Pregnancy Supportive care –prevent hypoglycemia -foetal monitoring -treat anaemia -antipyretics -antenatal care Intermittent preventive treatment for malaria in pregnancy (IPTp) Lactating Women: -Lactating women should receive standard anti-malarial treatment (including ACTs) except for tetracyclines which should be withheld during lactation. -Primaquine should not be used HIV and Malaria HIV and Malaria co-infection frequently occur with PF Transient ↑in viral load - wait for approx. 2 mths if used for monitoring HAART HIV associated with ↑susceptibility, higher parasitemia, and ↑risk for recurent Malaria particularly in patients with CD4counts <200/µl Dual infection in pregnancy → adverse maternal and perinatal outcomes- monthly IPT HIV and Malaria Suggest HIV testing in adults who present with clinical Malaria in endemic areas Treatment of Malaria in HIV infected is similar to HIV uninfected New infections may be higher in HIV +ve than in HIV negative and recrudescence of drug resistant parasites may occur. Close follow up. HIV and Malaria WHO recommends use of TrimethoprimSulfamethoxazole daily and bed nets in HIV infected patients with CD4 <200/µl ART ↓the incidence of Malaria therefore particular attention should be paid to administration of ART to those living in malaria endemic areas Treatment Of Uncomplicated Falciparum Malaria In Patients With HIV Infection Patients with HIV infection who develop malaria should receive standard anti-malarial treatment regimens as recommended. Treatment or intermittent preventive treatment with sulfadoxinepyrimethamine should not be given to HIVinfected patients receiving cotrimoxazole (trimethoprim-sulfamethoxazole) prophylaxis. ARVs and antimalarials Significantly impaired metabolism of Amodiaquin in presence of efavirenz, saquinavir, and ritonavir NNRT may compromise the therapeutic efficacy of quinine through induction of cytochrom p450 PI inhibit Cy p450 – co- administration of Halofantrine →cardiotoxic effect Some PIs have antimalarial activity- saq/rit Prevention of Malaria ITN Indoor residual spraying Repellant cream Chemoprophylaxis Environmental management VACCINE? MALARIA VACCINE The RTS,S vaccine. i.e. RTS,S/AS01E & RTS/ASO2D.-GlaxoSmithKline biologicals It is based on the circumsporozoite protein that targets the pre-erythrocytic cycle of Plasmodium falciparum in humans Induces pre-erythocytic immunity ,resulting in reduced number of merozoites released into the blood stream. RTS S VACCINE October 2011 Ist results on children aged 5-17months showed that 3 doses of the vaccine candidate reduced the number of malaria episodes over one year of follow up by 55%. November 2012 data for infants vaccinated aged 6-14 weeks showed estimated overall efficacy over 12months of follow up was 33% for all malaria episodes. rd 2013 3 set of results after 18months of follow up showed 27% efficacy against clinical malaria in 614weeks and 46%in 5-17months Rts s vaccine Data on efficacy of a booster dose will be out in 2014.WHO recommendation on use of the vaccine anticipated in 2015