Complicated Dengue And Malaria CRITICON-2010 DIU Mosquito….. Anopheles,Aedes Albopictus,Aedes Egypti Other Diseases spread by Mosquitoes: ■ ■ ■ ■ ■ 1) 2) 3) 4) 5) Rose River Virus:Australia:ChG Barman Forest Virus: -doMurray Valley Encephalitis:AUST:Fatal Japanese Encephalitis : Asia Via Pigs Chicken Guniya Dengue Virus ■ ■ ■ RNA Virus-Flaviviridae 4 subtypes Last year 50 lakh pts 5 lakh DHF mortality 2.5 to 25% Dengue Vectors: ■ ■ ■ ■ ■ ■ Female Aedes Egypti Stagnant clean water Thin rim of 50 paisa coin Female Aedes Albobticus In US EUROPE Used tyres Dengue Vectors ■ ■ ■ ■ ■ Incubation period 7-10 days Life span 3 wks Continuous spread in lifespan Vertical transmission to ova Eggs can remain in water for 1 year. Types: ■ ■ ■ ■ Asymptomatic DF DHF DSS ! ■ Primary And Secondary DF ■ Acute febrile illness >2 days with two or more of following 1) Headache 2) Retro Orbital Pain 3) Myalgia 4) Arthralgia 5) Rash 6) Hemorrhagic manifestation 7) Leucopenia PLUS: Supportive serology OR occurring at endemic dengue area. LAB DIAGNOSIS by WHO ■ ■ ■ ■ A) Isolation of Virus in autopsy B) >/= 4x rise in reciprocal IgG or IgM ab titers to one or more dengue virus antigen in paired serum sample. C) Antigen isolated in autopsy tissue,serum or CSF by IF/ELISA D) PCR Reliability of Tests ■ ■ ■ ■ Test sensitivity IgG+IgM 10-21% IgG+IgM EL 65% NS1 AG 72-81% specificity 88-98% 91-97% 100% ! ■ ■ IgM +ve only after day 4 in primary dengue NS1 helpful in early diagnosis. Tests: ■ ■ ■ IgG and IgM cross react with other Flavavirus high false +ve low specificity Low sensitivity in early days PRNT: Plaque Reduction and Neutralisation used to know which serotype DHF:Following all must be present…. ■ Fever or H/O fever lasting 2-7 days BIPHASIC with hepatomegaly ■ Hemorrhagic tendencies evident by.. * +ve Tourniquet Test * Petechia,Purpura,Ecchymosis * Bleeding from mucosa,Inj sites * GI bleed DHF :Cont.. ■ ■ Platelet count </= 1,00,000/cmm Plasma leakage causing one of following * Hematocrit rising >/= 20% of normal * Hematocrit falling to </= 20% of baseline following fluid replacement * Pleural effusions,Ascites,Hypoprotinemia Touriquet Test: ■ ■ Inflate BP cuff midway of SBP & DBP (100 if 120/80) for 5 min >/= 20 petechiae /Square Inch of skin PLATELETS ■ Rely on your eyes only 4-10 per oil emersion field NORMAL ■ </= 3/Oil emersion field is LOW ■ DSS ■ ■ ■ ■ ■ ■ DHF + Rapid weak pulse Narrow Pulse Pressure Hypotension Cold calmly skin restlessness GRADES ■ I: Fever+consttutional symp+positive torniquet ! ■ II : Spontaneous bleeding+Gr I ! ■ III : Shock,cold limbs,restlessness ! ■ IV: NO PULSE BP not recordable FINDINGS + (1-25%),++(26-50%),+++(51-75%),++++(>76% Finding DF Chick DHF Fever ++++ ++++ ++++ Tourni ++ +++ ++++ Petechia + ++ ++ Rash 0 + ++ Liver + 0 +++ ++++ MP Rash ++ ++ + Myalgia +++ ++ + LN ++ ++ ++ Low TC ++++ ++++ ++ Low PC ++ + ++++ Shock 0 0 ++ GI Bleed + 0 + Treatment: ■ ■ ■ ■ ■ Have to correct hematocrit Fluids+electrolytes Plasma/Whole blood/Fresh BT Colloids ORS Treatment cont… ■ ■ ■ ■ ■ Only PCM Critical phase starts as soon as fever subsides !! Admit all DHF,DSS Monitor hematocrit daily & sos from day 3 NaHCo3 reserved for pt with diarrhea I/V Fluids ■ Halliday & Segar formula wt fluid 10 100/kg 10-20 1 L+50/kg for each kg >10 1.5 L+20/kg for each kg>20 >20 Example 5% fl loss >20% hematocrit rise ■ ■ ■ ■ ■ ■ ■ ■ ■ Start I/V DNS 6-7 ml/kg/Hr . . . . improved Not Improved . . 5ml/kg/Hr 10 ml/kg/Hr 3 ml/kg/Hr 15 ml/kg/Hr stop aft 48 Hr Rapid i/v bolus Colloids,BT Rapid I/V Bolus ■ ■ ■ ■ ■ 10-20 ml/Kg/Hr in 20 min (1st) 20-30 ml/Kg/Hr in 20 min (2nd) 20-30 ml/Kg Colloid (3rd) If still hematocrit not falling give 5% albumin(10-20 ml/Kg) If hematocrit falls with hypotension it can be internal bleed-start BT Additional ■ ■ ■ ■ ■ ■ ■ Stress ulcers PPI Hyponatremia-kalemia Acidosis Over hydration Seizures ARF FHF Discharge ■ ■ ■ ■ ■ ■ ■ No fever > 24 Hr after DHF/DSS Good appetite Good U/O Stable hematocrit 2 days post hypotension recovery No Pl eff ascites good Spo2 PC >/= 50,000/cmm MALARIA MALARIA INTRODUCTION ■ ■ ■ Important cause of mortality in tropical countries. More than million/year die of malaria and its rising…. Chloroquine and SD+PY resistant in PF is now almost 100% CLINICAL DISEASE ■ ■ ■ ■ ■ Caused by P.Viavx,P.Ovale,P.Malaria,P.Falciparum and P.Knowlesi. Symptoms:Fever,Malaise,Headache,Lassitude,Fatigue, Chills,Perspiration,Anorexia,Volmiting and worsening malaise. Periodicity is typical in vivax. Prognosis depends on prompt diagnosis and early treatment. Delay increases chance of complications. Untreated severe malaria carries mortality of nearly 100%. Pattern of Malaria in community: ■ ■ Stable: community continuously exposed to malaria. African countries. High immunity, less complications. Complications mainly in less immune children and pregnant ladies. Unstable: Exposure has seasonal variations. Asian countries including India. Low immunity more complications. Malaria occurs in epidemics. Tratment Objectives: * Uncomplicated Malaria: Objective is to cure malaria. * Complicated Malaria: Objective is to save life and save organs…… Diagnosis: Clinical criteria & presence of MP in smear. ■ Clinical Diagnosis: * setting where risk is low:fever of 3 days and no other cause of fever * setting where risk is high:fever in previous 24 hr &/or presence of anaemia(pallor of palms most reliable in pediatrics) ■ Parasitological Diagnosis: ■ ■ ■ Sensitivity:Ability to find MP Specificity: Ability to find which type Objectives: to diagnose that pt has malaria and nothing else,To find other cause of fever when malaria excluded, preventing unnecessary use of antimalarials, Methods In Diagnosis: ■ ■ Light Microscopy: High Sensitivity in thick smear and high specificity in thin smear. Rapid Diagnostic Test(RDT): Uses antigen card Choice….Microscopy or RDT? ■ ■ Microscopy cheap and reliable but time consuming. One can know degree of parasitemia.Also can access WBC and platelets anomaly at same time. RDT expensive,fast.False results at high temperature and humidity. : ■ • • In Unstable Malaria: Microcsopy/RDT must for stamping fever as malaria. In stable Malria: Empirical treatment of any fever as malaria is justified. One can wait for diagnosis to confirm after starting treatment. Treatment of Uncomplicated falciparum malaria: ■ ■ ■ ■ Defined as symptomatic malaria without signs of vital organ dysfunction. To combat emerging resistance, combinations of drugs advisable. Combine two or more schizonticidal drugs with different mode of action to improve efficacy of treatment and reduce emergence of resistance. Standard combinations like SD+PY are considered single drug.Same way non antimalarial like CPM used to treat malaria is not considered combination. Rationale of Combination of antimalarials: ■ ■ ■ Combination more effective than single agent. In rare case of mutant parasite resistant to one drug, the second drug works. Disadvantage: more side effects and more cost. ACT:Artemisin based Combination Therapy ■ Artemisin and its derivatives artesunate,artemether,artemotil,dihydroartemisin produce rapid clearance of parasitemia and rapid resolution of symptoms. ! ■ They reduce parasitemia 10,000/sexual cycle(Quinine 100-1000) ! ■ They are rapidly cleared from body. ! ■ When combined with tetra/clinda long course of 7 days needed. ! ■ When combined with long acting agents 3 days course is enough. ! ■ Only adverse effect of artemisin compounds is urticaria. NON ACTS: ■ ■ ■ ■ ■ CQ+SP SP+AQ(Amodiaquine) Less efficacy and high resistance. Trials discourage use of SP+ CQ in PF Less parasite clearance with SP+AQ ACTS:Proved ■ ■ ■ ■ (1) (2) (3) (4) Artemether+Lumefantrine Artesunate+Amodiaquine Artesunate+ Mefloquine Artesunate+ SP ACTS not proved ■ ■ ■ ■ Chlorproguanil+dapsone Atovaquone+proguanil Aremisin+halofantrine Dihydroaremisin+piperaquine Artemether+lumefantrine ■ 20 mg of A+120 mg of L ! ■ Wt ! ■ 5-14 0h 8t 24h 36hr 48hr 60hr 1 1 1 1 1 1 15-24 2 2 2 2 2 2 3 3 3 3 3 4 4 4 4 4 ! ■ ! ■ 25-34 3 ! ■ >34 4 A+L ■ ■ ■ ■ Advantage: L never used alone and highly efficacious L better absorbed with fat.Low lavels with low fat diet,malabsorption. Always take with milk or fat containing food. Disadvantage: cost AS+AQ ■ ■ ■ ARTESUNATE 50 mg+ AQ 153 mg Dose: 2 BD x 3 days in adult Amodiaquine resistance go hand in hand with CQ resistance. AS+SP ■ ■ ■ ■ Artesunate 50 mg+ S 500 mg +p 25mg Artesunate 2 BD x 3 days SP 3 OD day 1 Resistance more as SP used alone in india as antimalarial cross resistance to TMP+S AS+MQ ■ ■ ■ ■ ■ AS 50 mg+250 mg MQ AS 2 BDX 3 days MQ: (4 )tab on day 2 and (2) tab on day 3 MQ cause gidiness,nausea,volmiting,dysphoria,sleep disturbance. Prior treatment with quinine-fatal arrythmias. Always treat full hearted ■ ■ Even if malaria is an empirical diagnosis not proved at lab and patient is given empirical antimalarials…..GIVE FULL COURSE. Artemisin compounds never used as single therapy. Patient with high parasitemia ■ ■ ■ More likely to develop complicated malaria. May need longer course of treatment Must be retaining oral medicines and complete full course. Supportive treatment ■ ■ ■ ■ ■ Tapid sponging:too cold water causes vasoconstriction and worsens fever. PCM:650 mg 4 to 6 hrly Antipyretics causes delayed parasite clearance due to reduced cytoadherance.But it also prevents vital organs!!!! Antiemetics Seizures:midazolam,lorazepam Treatment failure: ■ ■ ■ ■ ■ ■ ■ <2 wks:reinfection/recrudence. Has to be stamped by PS as RDT remain positive for weeks. Poor adherance to Rx,drug resistance, Treat with second line drugs > 2 wks:recrudence or new infection Retreat with firstline drugs. Don’t use mefloquine again:neuro-psy problems 2 nd line antimalarials: ■ ■ ■ Alternate ACT AS+doxy/tetra/clinda Quinine+doxy/tetra/clinda Special situations ■ ■ ■ ■ ■ ■ Pregnancy: More chances of low wt baby,anaemia,complications. Remains asymptomatic for many days. Safe AntiMalarials in 1st trimester: (Quinine,CQ,PG,S+P )with clindamycin Artemisins recommended in 2nd and 3rd trimester only. Best ARTEMISIN+CLINDAMYCIN for 7 days ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ Lactation: Dapsone and tetra contraindicated Travelers: Not immune,more complications AS+L,Q+tetra/clinda HIV: No change,avoid SP if pt on cotriamoxasole Malnourished: Malabsorption of oral, poor bioavailability of i/m because of poor muscle mass. Low albumin increases unbound drugs level. Tratment of complicated PF: ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ What is severe falciparum malaria? Clinically:Prostation Impaired consciousness Respiratory distress Multiple convulsions Circulatory collapse Radiological pul.edema Abnormal bleeding Jaundice Haemoglobinuria Lab tests: Severe anaemia Hypoglycemia Acidosis Renal impairment Hyperlactetemia Hyperparasytemia Treatment objective ■ ■ To prevent death…….. Secondary objectives: to prevent recrudence,resistance,transmission, disabilities. Antimalarials of choice in severe falciparum malaria ■ ■ Quinine Artemisin derivatives QUININE ■ ■ ■ ■ Loading 20mg/kg Maintainance 10mg/kg 8 hrly i/m is effective but painful. Can be administered P/R when parentral route not possible. Artemisin derivatives: ■ ■ ■ Artesunate is best as it is water soluble hence can be given i/v or i/m Proved superior to quinine in trials conducted. Erratic absorption of artemether following i/m injection. Artesunate ■ ■ 2.4 mg/kg is recommended dose ( 2 Vials in 50 kg pt) Has to be diluted in sodabicarb and dissolved in 5ml D5 and administered as soon as possible. Quinine: ■ ■ ■ ■ ■ Quinine best given i/v diluted each pint over 5-6 hrs. i/m over anterior thigh and not buttocks to prevent sciatic nerve injury.Split dose in each thigh 10mg/kg Adveffect:hypotension,hypoglycemia, deafness,blindness In altered RFT reduce dose to onethird form day 2 Artemisins never need dose adjustment in altered RFT/LFT F/UP: ■ ■ ■ ■ ■ After pt is stable start same drug in oral form and complete 7 days therapy. Add doxycycline for 7 days. In pregnancy add clindamycin for 7 days. After parentral one can use ACT. Avoid mefloquine. Treating complications: ■ ■ ■ ■ ■ ■ ■ ■ ■ ■ Coma: ABC Hyperpyrexia:sponging,antipyretics Convulsions: BNZ,Paraldehyde Hypoglycemia:25D,10D Severe anemia:BT ARDS:PEEP ARF:PD/HD Coagulopathy:FFP,Vit-K Metabolic acidosis:hemofiltration/HD Shock:inotropes exclude septicemia Trials of drugs…. ■ ■ ■ ■ ■ ■ ■ ■ ■ LMW dextran Heparin Steroids Pentoxiphylline TNF ALFA ANTIBODY Deferoxamine Adrenaline Hyperimmune serum Exchange BT During pregnancy: ■ ■ ■ Maternal mortality 50% Artesunate preferred to quinine in 2nd and 3rd trimester Artesunate to be avoided in 1st trimester. Hyperparasitemia ■ ■ ■ ■ More complications . 5% in unstable community and >10% in stable community. Oral Rx to those who are stable otherwise parentral 7 days course is sufficient Treatment of P.Vivax ■ ■ ■ 40% cases of malaria worldwide and dominates outside Africa. P.vivax in low transmission zone-less immune-all age groups. P.vivax and ovale can cause relapses. Chloroquine: ■ ■ ■ ■ ■ 25 mg/kg divided over 3 days. Combined with primaquin 0.25 mg/kg for 14 days. CQ resistant –Amodiaquin 30 mg/kg divided over 3 days.(= 10 mg/kg daily.) Moderate G6PD deficiency:Primaquine 0.75 mg/kg/week for 8 wks. ACT can be used against p.vivax .followed by primaquin.S+P based ACTS cant be used as p.vivax has resistance against S+P. Complicated P.Vivax: ■ ARDS,ARF,DIC can occur in p.vivax ! ■ ■ Cerebralmalaria, thrombocytopenia,pancytopenia,splenic rupture,jaundice,severe anemia can occur. Treatment should be same as complicated falciparum malaria.h ■ Breakthroughs into all the good things waiting for us can’t happen without break downs of all the old structures that are limiting us…….. ! ! ! ■ THANK YOU
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