Malaria, Något nytt att berätta?

Transkript

1 Malaria, Något nytt att berätta? Malaria minskar men fortfarande dödsfall Minskning med 25% sedan 2000 (I Afrika 33%) Test, Treat and Track! Diagnos före behandling Behandling bygger på Artemisininpreparat Sängnät, Indoor spraying Läkemedelsprofylax på tapeten igen! Vaccin inget genombrott Hot Artemisininresistens Pyrethrum resistens

2 Malaria Mal Aria dålig luft Beskriven 500 BC i Italien Hippokrates skiljde ut olika febrar: tertiana och quartana Kinaträdets bark; Mot feber i Peru upptäcktes av spanjorerna på 1600-talet, rek.av Linné mot frossa 1880-talet: Myggor för med gift från sumpmarker Kring 1900 malariacykeln fastställdes Malaraläkemedel krigens läkemedel 1930 talet Klorokin anv. av amerikaner talet Proguanil (Paludrin), Pyrimethamin (Daraprim) Sulphonamide+Pyrimethamine (SP eller Fansidar) 1970 talet Meflokvin (Lariam) 1990 talet Atovaquone+ Proguanil (Malarone) Artemesininpreparat

3 Malariaprogram Malaria eradication tal Malaria control tal Roll Back Malaria Halvera morbiditet och mortalitet i malaria 2010 jämfört med år 2000 Abudja deklarationen 2000 Global Fund to Fight AIDS, TBC and Malaria Bill Gates donation 2011 nya mål Malaria dödlighet i Afrika minskar

4 Roll Back malaria- Nya mål 2011 (RBM) targets were updated in June reduce global malaria deaths to near zero by end 2015; reduce global malaria cases by 75% from 2000 levels by end-2015; and eliminate malaria by end 2015 in 10 new countries since 2008,

5 Malaria miljarder US dollar för malaria kontroll 2012 Beräknat behov 5,1 miljarder USD

6 Malaria 2012 Antal fall i världen 220 milj Döda % av hushåll i Sub Saharan Afrika har myggnät. De används i 95 % av dessa Metoder att minska malariasjuklighet Effektiv behandling LongLasting Insecticide Nets Pyrethroids Indoor spraying IPTp till gravida och små barn IPTi (SP)

7 Malaria Hot Minskande eller otillräckliga resurser Resistens mot insekticider särskilt pyrethroids (enda medel i LLIN) Har påvisats i 64 länder med malaria transmission Resistens mot Artemisin Har påvisats i Thailand, Cambodja, Burma och Vietnam

8 Roll Back Malaria Test Alla fall ska ha en säker diagnos Snabbtest eller Microskopi Treat Behandla med effektiva antimalariamedel i Afrika; Artemisinin PREPARAT Track Öka ansträngningar att förhindra nya fall Bednets, Indoor spraying, profylax

9 AKTUELLA DOKUMENT

10 The artemisinin story In the tomb of the Han nobleman, "Marquis of Dai", living 2200 years ago. Chairman Mao : Find new treatment of malaria! The chinese army had a problem in the Vietnam war 1972; Tu Youyou discovered artemisinin in the leaves of Artemisia annua (annual wormwood; kinesisk sommarmalört). The drug is named Qinghaosu in Chinese. It was one of many candidates then tested by Chinese scientists from a list of nearly 200 traditional Chinese medicines for treating malaria. It was the only one that was effective, but it was found that it cleared malaria parasites from their bodies faster than any other drug in history.

11 Artemisinin derivat Artemether Riamet=artemether lunefantrin ( I Tanzania-ALU) Artesunate Artemotil Dihydroartemisinin Kombinationer; artesunat+amodiaquine eller mefloquine eller SP

12 Artemisininderivat vs Kinin

13 Severe malaria Severe malaria is most commonly caused by infection with Plasmodium falciparum, although P. vivax and P. knowlesi can also cause severe disease. The risk is increased if treatment of an uncomplicated attack of malaria caused by these parasites is delayed. Recognizing and promptly treating uncomplicated malaria is therefore of vital importance Sometimes, however, especially in children,severe P. falciparum malaria may develop so rapidly that early treatment of uncomplicated malaria is not feasible.

14 Severe malaria Clinical features of severe malaria impaired consciousness (including unrousable coma); prostration, i.e. generalized weakness so that the patient is unable to sit, stand or walk without assistance; multiple convulsions: more than two episodes within 24h; deep breathing and respiratory distress (acidotic breathing); acute pulmonary oedema and acute respiratory distress syndrome; circulatory collapse or shock, systolic blood pressure < 80mm Hg in adults and < 50mm Hg in children; acute kidney injury; clinical jaundice plus evidence of other vital organ dysfunction; and abnormal bleeding.

15 Severe malaria- lab findings hypoglycaemia (< 2.2mmol/l or < 40mg/dl); metabolic acidosis (plasma bicarbonate < 15mmol/l); severe normocytic anaemia (haemoglobin < 5g/dl, packed cell volume < 15% in children; <7g/dl, packed cell volume < 20% in adults); haemoglobinuria; hyperlactataemia (lactate > 5mmol/l); renal impairment (serum creatinine > 265μmol/l); and pulmonary oedema (radiological). Hög andel smittade röda blodkroppar. >2.5% ökar risken men i högendemiska områden kan man se 20%

16 Severe malaria Pl Falciparum but also Pl Knowlesis Microscopy is gold standard Few parasites does not rule out severe mal. Where microscopy is unavailable or unfeasible, a rapid diagnostic test (RDT) should be used. RDTs for detecting HRP2 antigen can be useful for diagnosing malaria in patients who have recently received antimalarial treatment and in whom bloodfilms are transiently negative for malaria parasites. If both the slide and the RDT are negative, the patient is extremely unlikely to have malaria

17 Severe Malaria Make a rapid clinical assessment, with special attention to the general condition and level of consciousness, blood pressure, rate and depth of respiration and pallor. Assess neck stiffness and examine for rash to exclude alternative diagnoses. Admit the patient to an acute illness ward or room; or next to the nurses station in a general ward for close monitoring. However if indicated and available, admit the patient to an intensive care unit. Make a rapid initial check of the blood glucose level, correct hypoglycaemia if present, and then monitor frequently for hypoglycaemia.

18 Severe Malaria -Hypoglucaemia If hypoglycaemia (threshold for intervention, 3mmol/l) is detected by blood testing or suspected on clinical grounds, give Adults: - 25g of dextrose (preferably as 10% dextrose) over a few minutes.. Children Immediately give 5ml/kg of 10% dextrose through a peripheral line, and ensure enteral feeding or if not possible maintain with up to 5ml/kg per hour of 10% dextrose.. Continue to monitor blood glucose levels (with a rapid stix method if available) in order to regulate the dextrose infusion. Remember that hypoglycaemia may recur even after treatment with intravenous dextrose.

19 Artesunate new recommendation april 2011 The AQUAMAT trial, Lancet 2010; 376: a multi-centre study conducted in African children hospitalized with severe malaria. This very large randomized controlled trial, which enrolled 5425 children < 15 years of age across Africa, a significant mortality reduction by 22.5% in the artesunate group when compared to the quinine group. The incidence of convulsions, coma, and hypoglycaemia developing after hospital was also significantly reduced. Importantly there was no significant difference in the incidence of severe neurological sequelae

20 Severe malaria anti malaria treatment For adults and children, 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. Artemether, or quinine, is an alternative if parenteral artesunate is not available: artemether 3.2 mg/kg BW IM given on admission then 1.6 mg/kg BW per day ; or quinine 20 mg salt/kg BW on admission (IV infusion or divided IM injection), then 10 mg/kg BW every 8 h; infusion rate should not exceed 5 mg salt/kg BW per hour. Give parenteral treatment for 24 h. complete treatment by giving a full course of oral artemether plus lumefantrine or other available combination Broad spectrum Antibiotics also indicated to all cases of severe malaria

21 Pre referral treatment of severe malaria If complete treatment for severe malaria is not possible patients with severe malaria should be given pre-referral treatment and referred immediately to an appropriate facility for further treatment. The following are options for pre-referral treatment: rectal artesunate quinine IM artesunate IM artemether IM. In young children of less than 5 years of age, the use of the use of rectal artesunate (10 mg/kg) has been shown to reduce the risk of death and permanent disability.

22 Severe malaria pregnant women Increased risk Hypogkucemia and pulmonary oedema Mortality rate 50% Artesunate is the drug of choice. If this is not available, artemether is referable to quinine in later pregnancy because quinine is associated with a 50% risk for hypoglycaemia

23 Severe malaria-seizures Treat seizures with a benzodiazepine (intravenous diazepam,). If a seizure episode persists longer than 10min after the first dose, give a second dose of a benzodiazepine Total dose benzodazepim 1 mg/kg per 24 h Seizures that persist (status epilepticus) despite the use of two doses of benzodiazepam, give phenytoin Phenytoin (Epanutin) 18mg/kg body weight intravenously, or Phenobarbitone (Fenemal)15mg/kg body weight intramuscularly or intravenously if it is the only available option. Monitor breathing repeatedly. High dose of phenobarbitone (20mg/kg body weight) has been linked to an increased risk for death and the patient may need assisted ventilation.

24 Treatment of uncomplicated malaria Artemisinin-based combination therapies (ACTs) are the recommended treatments for uncomplicated P. falciparum malaria. Fixed combinations för three days artemether plus lumefantrin ALU (Riamet) Adults 4 tabl 6 trimes 0,8,24,36,48 and 60 h The recommended treatment is a 6-dose regimen over a 3-day period. (5 14 kg: 1 tablet; kg: 2 tablets; kg: 3 tablets; and > 34 kg: 4 tablets), given twice a day for 3 days. Other ACT artesunate plus amodiaquine, artesunate plus mefloquine, artesunate plus sulfadoxine-pyrimethamine, dihydroartemisinin plus piperaquine.

25 Malaria - behandling Nytt hopp för Klorokin?? Malawi var 50% av allla Pl falc. Resistenta 1993 mot klorokin Helt stopp i användningen av klorokin Molekylär markör för klorokinres borta jmf studie 210 barn medd okomplicerad malaria. Klorokin failure 1 /80. Fansidar failure 71/87

26 Malariavaccin RTS S vaccin Sporocoitantigen kopplat till HBsAg och adjuvans AS01 Utvecklat av GSK Melinda o Bill Gates har satsat miljarder

27 Malariavaccin projekt

28 Malaria vaccin Strategic goal By 2025, develop and license a malaria vaccine that has a protective efficacy of more than 80% against clinical disease and lasts longer than four years. Landmark By 2015, develop and license a first-generation malaria vaccine that has a protective efficacy of more than 50% against severe disease and death and lasts longer than one year.

29 The current status of malaria vaccine research WHO Nov 2012 No licensed malaria vaccines. Over 20 vaccine in clinical trials. The vaccine RTS,S/AS01 against Plasmodium falciparum, with no protection expected against P. vivax malaria. a partnership between GlaxoSmithKline Biologicals and Malaria Vaccine Initiative (MVI), with funds from the Bill & Melinda Gates Foundation. The clinical testing of RTS,S is at least 5-10 years ahead of other candidate malaria vaccines.

30 Malariavaccin RTS,S/AS01 Sporocoitantigen Hepatit B s antigen (HBsAg) Ny och potent adjuvans Fas 3 studie startade barn inkluderade Sju länder i Sub-Saharan Africa Kontrollgruppen fick Meningokock eller Rabies vaccin

31 RTS,S/AS01 delstudie 5-17 mån vid dos 1 3 doser 1 mån intervall Follow-up 12 mån efter sista dos N Engl J Med 2011; 365: Nov Incidence of the first or only episode of clinical malaria was 0.44 per person-year in the RTS,S/AS01 group and 0.83 per person-year in the control group (Rabies vaccin, per protocol analysis) efficacy against clinical malaria 55.8% severe malaria 47.3% The efficacy over a 4-year period was 16.8%. Efficacy declined over time and with increasing malaria exposure. (Tidig studie i Kenya) Ingen skillnad i dödlighet mellan grupperna Samma frekvens biverkningar men fler krampanfall i RTS,S gruppen

32 RTS,S/AS01, delstudie 6-12 veckor vid dos 1 3 doser, 1mån intervall Follow up 12 mån efter första dos N Engl J Med 2012; 367: December 13, 2012 The incidence of the first or only episode of clinical malaria was 0.37 per personyear in the RTS,S/AS01 group and 0.48 per person-year in the control group, (Meningokockvaccine, per protocol analysis) efficacy against clinical malaria 31.3% against severe malaria 36.6% Adverse events similar frequency Meningitis 9/4358 vs 2/2179