PowerPoint Presentation

Case-based SeminarMalariaWin Yupar Lwin (Roll No. 407)Win Shwe Sin Oo (Roll No. 408)Win Lei Khine (Roll No. 409)10th December, 2015Ward 17/18, YGH, 3rd bloc posting

History

Personal IdentificationName Aung Than HtutAge 23 yrsRace & religion Mon, BuddhistMarital status married, 1 childAddress YayOccupation Rubber tapper ()Education- passed 6th standard Date of admission 8th December, 2015

Chief ComplaintFever x 8 days

History of Present IllnessFever x 8 days duration

High grade, 104FContinuousChills & rigor (+)T to 102F by tepid spongingNo evening rise of T

HOPI continuedFever is associated with skin rash (+) in both upper & lower limbsNo mucosal bleeding such as nose bleeding, gum bleeding, vomiting of blood & passing of black tarry stool

HOPI continuedJoint pain (+)Muscle pain (+)No abdominal pain & distension

Headache x 5 daysGeneralized in characterWorsen at the height of temperatureNo fits, loss of consciousnessNo agitation, restlessness, disorientation

HOPI continuedNausea (+)Vomiting x 3 days (2 times/day)Amount about 150 ml each timeColour yellow & green vomitusContent everything he ate, no blood Taste bitter

System ReviewCVS NO palpitation, dyspnoea, orthopnoea, chest pain, syncopeRespiration NO breathlessness, cyanosis, cough, haemoptysisGI nausea (+), vomiting (+), NO diarrhoea, constipation, abdominal pain, jaundice Renal NO frequency, urgency, haematuria, oliguria, loin pain

CNS headache (+), NO tingling or numbness, weakness of both upper & lower limbs, fits, change in sensorium, projectile vomitingHaematological lassitude (+), skin rashes (+) on both upper & lower limbs, NO mucosal bleeding, pallor, tiredness, breathlessness on exertion, recurrent infection, swelling in neck, groin, axillaMusculoskeletal joint pain (+), muscle pain (+)

After admissionBlood tests, urine test, USG are doneResults are not known

In ward oral medication 9 tablets/day - 1 bottle of infusionNames of medication are not known

No significant improvement, no vomiting since admission

Past Medical HistoryNo history of similar attackNo history of hypertension, DM, heart d/s, TB

History of typhoid fever last yearHospitalized for 2 days at Yay General Hospital

History of Hepatitis (unknown type) last year 3 months after typhoid fever Hospitalized for 2 days

Past Surgical HistoryNo history of surgical operationNo history of blood transfusion

Drug HistoryNo regular taking of drugs History of taking indigenous medicine for indigestion frequently for about 1 yrNo known drug allergy

Family History

2 family members No history of similar attack in familyNo family history of TB, hypertension, DM, heart d/s

Personal & Social HistoryAlcohol drinking Since 13 yrs of age, cut off 4 yrs ago (duration~ 6 yrs)3-4 cups of toddy palm sap () per daySmokingSince 13 yrs of age, cut off 4 months ago1 cheroot per dayBetel chewingSince 16 yrs of age, cut off 3 yrs ago5 pieces per dayIncome is enoughPlenty of mosquito breeding places near the house

Physical Examination

General examinationYoung aged gentleman is lying on the bedNutritional status - thin for his ageHe looks ill, well conscious, well orientatedNot dyspnoeic

General examination contd.High fever (+)Mild pallor (+)Tinge of jaundice (+)Subconjunctival hemorrhage (+)Eyeball tenderness (+)No active epistaxisNo central cyanosisNo angular stomatitis, no glossitis, no active gum bleedingBetel staining (+) on teethNo visible neck gland enlargement

On examination of upper limbsCannula (+) on left handSkin rash (purpura) (+) on both handsNo clubbingNo leukonychia, No koilonychiaNo palmar pallor, no palmar erythemaNo Dupuytren's contractureNo flapping tremor

On examination of lower limbsNo clubbingNo pitting oedemaSkin rash (purpura) (+) on both legsCalf muscle tenderness (+)

Abdomen Examination On inspectionAbdomen is flat Moves with respirationFlanks not fullUmbilicus normalNo scars, no dilated veinsNo scratch marks, no radiation marksHernia orifices intact

Abdomen examinationOn palpation

Light Palpation

Abdomen is soft, not tenderNo guarding, No rigidityNo palpable mass

Abdomen examinationDeep palpation

Liver is palpable in RHC3 cm below the right costal margin in the right mid-clavicular lineSharp edgeSmooth surfaceFirm in consistencyNo tendernessCannot insinuate between the costal margin & massNo upward enlargementSpleen is not palpableKidneys are not ballotable

Respiratory systemRR= 18 breaths/minVesicular breath sound is heard in all 3 zones of both lungs with no added sounds

Cardiovascular systemBP= 110/60 mmHgPR= 100 beats/minNormal 1st & 2nd heart sound with no added sounds

Central Nervous systemTone of both upper & lower limbs are normalPower 5/5 normalNo facial palsy, no neck stiffness

No generalized lymphadenopathy

Differential DiagnosesMalariaLeptospirosisTyphoid feverAVI/DHF

Investigations

Temperature chart

Full blood countWBC11.9x 109/L Lympho1.8 x 109/L Mid#0.5x 109/L Gran#9.6x 109/L

Hb13.5 g/dlESR 45 mm/1st hr RBC5.6x 1012/L HCT 0.428L/L MCV76.6 fL MCH24.1pg MCHC31.5g/dl

PLT144x 109/L

Liver Function TestTotal bilirubin9mol/LALT 80U/L AST100U/L Alkaline phos.91U/L

Albumin30g/LGlobulin40g/LTotal protein70g/L

Urea & ElectrolytesUrea 4.8mmol/LCreatinine94mol/LNa123mmol/L K3.4mmol/LCl84.6mmol/L Bicarbonate 28.7mmol/L

UrinalysisSG1.005pH 6LeucocytenegativeNitrite negativeProtein100 (2+)GlucosenormalKetonenegativeUrobilinogen normalBilirubinnegativeBlood250 Ery/dl (4+)

Infection Screening6/12/2015 Yay private hospitalHBsAgReactiveHCVNon-reactiveRetro viral testNon-reactive

Chest X-ray6/12/2015 - Yay

CT ratio normal Hila not enlargedSlightly increased markings on both lungs

Finding:Bronchitis

Ultrasound Abdomen6/12/2015 - YayLiverReduced echo Normal sizeSmooth surfaceSpleen Enlarged, 12.2 cm lengthGB & biliary tractPancreasKidneysBladderImpressionMild hepatitisMild splenomegaly

Normal

Ultrasound Abdomen9/12/2015 - YGHLiverNormal echo & sizeSharp edgeSmooth surfaceGB & biliary tractNot dilatedNo SOLSpleen & PancreasAppear normalKidneysNormal, no stonesBladderSlightly distendedImpressionNo obvious abnormality detected

For DDx Leptospirosis Leptospiral Ab IgGNegativeLeptospiral Ab IgMNegative

For DDx Widal reportO. agglutininH. agglutininSalmonella tryphiNegativeNegativeSalmonella paratyphi ANegativeNegativeSalmonella paratyphi BNegativeNegative

For DDx AVI Hess test PositiveNS1AgNegativeDengue Blot IgG Not detectedDengue Blot IgMNot detectedHess test PositiveNS1AgNegativeDengue Blot IgG Not detectedDengue Blot IgMNot detected

Current Medical Treatment

D/S2 bot, 20 dpm on admissionIV Ceftriaxone 1 G, 12 hrlyORS2 L/dayPO Hepacel1 tab, bdPO Mirax1 tab, tds PO Para1 tab, tdsIV C. pen20 L, 6 hrlyIV Artesunate2 amp stat, & 12, 24, 48, 2 tab od x 6 daysPO Doxycycline100 mg, bd x 7 days

MalariaLiterature Review

Causal organismSystemic protozoal infection caused by

Plasmodium falciparum (malignant tertian)Plasmodium vivax(benign tertian)Plasmodium ovale(benign tertian)Plasmodium malariae(benign quartan)Plasmodium knowlesi (monkeys)

Mode of transmissionVector borne (Sporozoite induced malaria)Transfusion (Trophozoite induced malaria)IVDU (inoculated malaria)Transplacental (congenital malaria)

Vector

Female Anopheles mosquitoAnophelus dirusAnophelus minimusAnophelus maculatusAnophelus aconitusAnophelus sundiacus

Life cycle of malaria parasite in human host

RelapseOnly in P. vivax & P. ovaleSome sporozoites go under resting phase in liver, instead of preceding further in the cycleLater forms hypnozoites & gives rise to various symptomsEnables survival during cold wintersIf re-activated new focus of transmissionRecrudescenceAll speciesDue to failure of elimination either by immune system or treatment failureNo clearance of parasitemia but reduced to sub-patent levels for a timeA period of 8 weeks is needed to exclude recrudescence of drug-resistant parasites

Affected RBCsP vivax, P ovale young RBCsP malariae old RBCsP falciparum RBCs of all ages

***Genetic resistance to malariaRace : NegroGenetic : G6PD deficiencyHaemoglobinopathies : Resistant toHb C or EP. falciparumSickle cell anaemiaThalassaemiaHereditary elliptocytosisDuffy blood group negative RBC (resistant to P. vivax)

Clinical FeaturesProdromal symptomsHeadache, photophobia, muscle ache and pain, anorexia and vomitingCold stageSudden shaking chills or rigor, pale and cyanotic10-15 min Hot stageFlushed, agitated, restless, disoriented, deliriousSevere frontal headache, pain in limbs and back2-4 hrsSweatingProfuse sweating weak and exhaustedSeveral hrs

PHYSICALSIGNS

Complications of Falciparum malariaAlgid Malaria (SBP 90% of cases, the species of parasite can also be identified.Simply fill a capillary tube with a patient sample coat with acridine orange (fluorescent dye) centrifuge place under a fluorescent microscope Detects additional 4 % of the malaria cases

5) DNA detection (PCR)Used mainly in researchUseful for determining whether a patient hasa recrudescence of the same malaria parasite ora re-infection with a new parasite

Treatment of Malaria

Artemether + LumefantrineTotal dose of 5-24 mg/kg Artemether + 29-144 mg/kg LumefantrineRecommended dosage regimen twice a day for 6 days (total 6 doses)1st two doses should be given 8hrs apart ideally.Advantage of this ACT is that lumefantrine is not available as monotherapy and has never been used as alone for malaria treatmentAbsorption of Lumefantrine is enhanced by co-administration with fat, thus should be taken immediately after food.

Artesunate + AmodiaquineTarget dose: 4 mg/kg/day (2-10) IV Artesunate + 10 mg/kg/day (7.5-15) AmodiaquineOnce a day for 3 daysSide effect of severe neutropenia in patients co-infected with HIV, esp with those on Zidovudine and/or Cotrimoxazole.

Artesunate + MefloquineTarget dose: 4 mg/kg/day (2-10) Artesunate + 8.3 mg/kg/day (5-11) MefloquineOnce a day for 3 daysMefloquine is associated with severe nausea & vomiting, dizziness, dysphoria, sleep disturbanceTreatment failure frequently occurs in patients taking Rifampicin

Artesunate + Sulfadoxime-PyrimethamineTarget dose: 4 mg/kg/day (2-10) Artesunate (od x3days) + at least 25/1.25 mg/kg Sulfadoxime-Pyimethamine single dose on day 1Disadvantage of this combination is that it is not available as fixed dose combination, reducing the compliance & adherence of patient to the drugsResistance is increasing due to widespread use of S-P.

Dihydroartemisinin-PiperaquineTarget dose: 4 mg/kg/day (2-10) Dihydroartemisinin + 18 mg/kg/day (16-27) PiperaquineOnce a day for 3 daysHigh fat meals should be avoided as it increases the absorption of Piperaquine, thereby increasing the risk of potentially arrhythmogenic delayed ventricular repolarization (ECG prolonged QT interval)Treatment failure is very common in young children & pregnant women

FDCsRiamet/Coartem(artemeter+lumefantrine)S/E : GI irritation/long QT/ palpitation/dizzinessCI: H/o of heart d/s, family h/o of sudden death, long QT

Malarone(proquanil+atovaquone)SE: GI irritation

Quinoline derivativesQuinine (1 tab=600 mg, 1 ampoule= 1 ml= 600 mg)Indication: severe and complicated malaria in CQ resistance area and wherever the sensitivity is unknown (safe in pregnancy)Contraindication: Loading dose should not be used in those patients who have received quinine or mefloquine within previous 24 hoursSide-effects: 1. Cinchonism (nausea, vomiting, abdominal pain, blurred in vision, transient loss of hearing, vertigo and tremors)2. overdose: convulsion, hypotension, heart block, ventricular fibrillation3. hyperinsulinaemia: hypoglycaemia

Fansidar (Sulfadoxine-pyrimethamine)(1 tab=525 mg)

Indication: clinically suspected malaria, uncomplicated falciparum malariaContraindication: hypersensitivity to sulpha, pregnancy, neonateSide-effects: GI-nausea, vomitingSkin-mild to severe rash (Steven Johnsons syndrome)Anaemia, leucopenia, intravascular haemolysis in G6PD deficiency

Management of severe complicated malariaTreatment of choice is IV Artesunate 2.4 mg/kg at 0,12,24 hrs and once daily for 7 daysTotal cumulative dose of 17-17 mg/kg

Management of Complications

ALGID MALARIARapid development of hypotension and impairment of vascular perfusionSymptoms of generalized vascular collapse and shock develop quicklyThis syndrome may be as a result of Hot phaseGram negative septicaemia?Uncorrected dehydrationHaemorrhage from GI and splenic rupturePulmonary oedemaTreatment: initial therapy involves correction of haemodynamic problems and administration of antibiotics

Black water feverMassive intravascular haemolysis and consequent haemoglobinuriaIt is associated with chronic falciparum malaria, most commonly in those who have taken antimalarial drugs irregularly are deficient in G6PDIt has been speculated that it represents an autoimmune phenomenon with development of antibodies to infected RBC.Relationship between black water fever and use of quinine but quinine therapy should not be discontinued if black water fever develops.

Cerebral malariaAny impairment of consciousness or convulsion in patient exposed to malariaDue to sequestration of parasitized RBC in microcirculation of CNS, leading diffuse cerebral encephalopathy including cerebellum.Associated with hyperparasitaemia and 5% in immune patients and who are non immune with more than 1% red cells infected.

Disseminated Intravascular CoagulationDue to adherence of parasitized RBC to endothelium of capillary or Gram negative septicaemia.Present as severe bleeding manifestation

EnteromalariaCholeric type (diarrhoea)Due to GI mucosa oedema due to capillary leakage leading diarrhoeaDysenteric malariaAbdominal pain, nausea, vomiting and upper abdominal (gastrointestinal) haemorrhage which may be related to focal ischaemic changes, intestinal wall capillary bed.Bilious remittent feverLiver enlarge and tender, the skin is icteric and the urine contains bile due to focal necrosis and oedema in liver cells due to microcirculatory damage.

Fluids and Electrolyte imbalance and Metabolic acidosisPlasma leakage leading to hypovolaemia and electrolyte imbalanceHypovolaemia, capillary occlusion leading to poor tissue oxygen delivery and lactic acidosis

Gram negative SepticaemiaIntestinal congestion, focal ischaemic change to breakdown of gut mucosa barrier, possibly leaky to Gram negative bacteria causing septicaemia which turn to cause Hypotension and hypoglycaemia

HypoglycaemiaImportant complication resulting fromGram negative septicaemiaHyperinsulinaemia due Quinine therapyImpairment of hepatic gluconeogenesisCommon in children and pregnant women causing increase death rate

HyperparasitaemiaParasitaemia in excess of 10-20% of red blood cells carry high mortality rate despite prompt and vigorous treatment.Treatment: prompt exchange blood transfusion may be life saving in these circumstances

HyperpyrexiaTemperature >41.C can cause heat stroke.

Malaria anaemiaDue to Haemolysis of infected and uninfected RBCDyserythropoiesisSplenomegaly causing erythrocyte sequestration and haemodilutionQuinine therapyDepletion of folate storeTreatment: Prevent overload if haematocrit fall below 20% or if there is parasitaemia of 5% or greater.Exchange transfusion

Obstetric complicationMaternal deathAbortionStill birth weightPrenatal death

Pulmonary oedemaPulmonary oedema may develop rapidly in oliguric or anuric patient, secondary to overzealous parenteral administration or cardiac decompenstion as a result of DIC or anoxic effect of pulmonary microcirculationTreatment: should receive the same medical management as pulmonary oedema or ARDS in critically ill patient.

Renal failureAcute renal failure as a result of Acute tubular necrosis resulting from red cell slugging and renal anoxiaTreatment: fluid balance, dialysis may be needed

Splenic ruptureSplenomegaly result, prone to get trauma which can lead to intraperitoneal haemorrhage and shock

Tropical splenomegaly syndorme (TSS)The spleen normally enlarge during an acute attack of malaria but then regresses towards normal, so persistent splenomegaly in adult is not normal finding.TSS is characterised by chronic splenomegaly and marked elevation of serum immunoglobulin MIgM aggregates are phagocytosed by RE cells in spleen and liver.Anaemia and lymphocytosis can be confused with leukaemiaTreatment: continuous with proguanil 100 mg daily with folic acid 5 mg daily`

Drug resistanceS: clearance of parasite within 7 days without subsequent recrudescenceR1: clearance of parasite within 7 days but recrudescence after 28 daysR2: parasite clearance > 75% within 7 days but no complete clearanceR3: no reduction of parasite

Global malarial resistance since 1960

Nobel prize winners

ReferencesDavidsons Principles & Practice of Medicine, 22nd edition, 2014 Infectious diseases Systemic Protozoal Infections Malaria WHO guideline for treatment of malaria, 3rd edition, 2015Worldwide Antimalarial Resistance Network (WWARN)

Thank youfor your attention!