Malaria – Filling in the Malaria – Filling in the blanks !blanks !

Dr Gaurav GuptaDr Gaurav Gupta

MAAP, MIAP, DCH, DNBMAAP, MIAP, DCH, DNBCharak Clinics, MohaliCharak Clinics, Mohali

Malaria is more deadly than swine fluMalaria is more deadly than swine flu

H1N1 swine flu has killed 180 people worldwide. H1N1 swine flu has killed 180 people worldwide. And around 45,000 cases reported world-wide (June And around 45,000 cases reported world-wide (June 19th).19th).

WHO estimates that 3,000 people a day die from WHO estimates that 3,000 people a day die from malaria in Africa every day, mostly women and malaria in Africa every day, mostly women and childrenchildren

Unlike influenza, we have no vaccine against malaria. Unlike influenza, we have no vaccine against malaria. Now resistance to the MOST effective anti-malarial Now resistance to the MOST effective anti-malarial

Artemisinin is being reported from Cambodia – we Artemisinin is being reported from Cambodia – we have nothing left after this.have nothing left after this.

Deadly StatsDeadly Stats

Nearly half of the world's Nearly half of the world's population, or about 3.3 billion population, or about 3.3 billion people, are at risk of malarial people, are at risk of malarial infection, infection,

It causes more than 250 million clinical episodesIt causes more than 250 million clinical episodesOne million deaths each year. One million deaths each year. Pregnant women, under 5 children, and first-Pregnant women, under 5 children, and first-timers have more complicated infections. timers have more complicated infections. Kills one child every 20 secondsKills one child every 20 seconds

Malaria - BasicsMalaria - Basics

Four speciesFour species Transmitted by female Transmitted by female

anopheles anopheles No. 1 priority tropical No. 1 priority tropical

infectious disease according infectious disease according to WHOto WHO

Incidence is increasing by 16 Incidence is increasing by 16 % every year.% every year.

No. 3 killer infectious disease No. 3 killer infectious disease in the worldin the world

India – 15,24,939 / 49 % India – 15,24,939 / 49 %

State/YrState/Yr 20022002cases/ p flcases/ p fl

20062006

cases/ p flcases/ p fl

20082008

cases/ p flcases/ p fl

HaryanaHaryana 936/41936/41 42991/19942991/199 35683/139735683/1397

PunjabPunjab 250/18250/18 1650/231650/23 2494/382494/38

ChandigarhChandigarh 157/6157/6 377/3377/3 347/6347/6

DelhiDelhi 694/6694/6 593/5593/5 253/0253/0

Clinical FeaturesClinical Features

Fever – atypical patternFever – atypical pattern Headache, body ache, altered sensorium, Headache, body ache, altered sensorium,

cough breathlessness, acute abdomen pain, cough breathlessness, acute abdomen pain, vomiting, diarrheavomiting, diarrhea

Malaria can mimic almost Malaria can mimic almost

anything and everything !anything and everything !

DiagnosisDiagnosis

Microscopy – Thin Smear for Microscopy – Thin Smear for species & stage identificationspecies & stage identification

Microscopy – Thick Smear for Microscopy – Thick Smear for detection of MP & for the detection of MP & for the degree of parasitemiadegree of parasitemia

Non microscopy – RDT – May Non microscopy – RDT – May have lower sensitivity, more have lower sensitivity, more sensitive for P. Falciparumsensitive for P. Falciparum

Diagnosis - RDTDiagnosis - RDT

RDT – Pros & ConsRDT – Pros & Cons

High sensitivity, good specificity, reliable for P. High sensitivity, good specificity, reliable for P. Falciparum, may be positive when a smear is negativeFalciparum, may be positive when a smear is negative

Expensive, does not differentiate mixed infections, Expensive, does not differentiate mixed infections, cannot be used to judge therapeutic response, does cannot be used to judge therapeutic response, does not measure severity of infection, still may have false not measure severity of infection, still may have false positive and negativespositive and negatives

Consensus: Use it in conjunctionConsensus: Use it in conjunctionwith PBF (thick and thin smears)with PBF (thick and thin smears)

Interesting fact!Interesting fact!

Widal test Widal test may be positive, even up to a may be positive, even up to a dilution of 1:320 for 'O' and H' and at lower dilution of 1:320 for 'O' and H' and at lower titres for 'AH' and 'BH'. Any or all the four titres for 'AH' and 'BH'. Any or all the four may be positive, suggesting a non-specific may be positive, suggesting a non-specific response. response. A positive Widal test in a patient A positive Widal test in a patient with confirmed malaria should not therefore be with confirmed malaria should not therefore be considered as suggestive of typhoid fever. considered as suggestive of typhoid fever.

Hold the third finger of the left hand and wipe its tip with spirit/Savlon swab; allow to dry

Prick the finger with disposable needle/lancet; allow the blood to ooze out

Take a clean glass slide. Take 3 drops of blood 1 cm from the edge of the slide, take another drop of blood one cm from the first drop of blood

Take another clean slide with smooth edges and use it as a spreader

...and make thick and thin smears. Allow it to dry

Prepared smear. Slide number can be marked on the thin smear with a lead pencil.)

Chloroquine (PO/IV)Chloroquine (PO/IV)(150 mg Base/ Tablet(150 mg Base/ TabletSyp 50 mg/ 5ml Base)Syp 50 mg/ 5ml Base)

(LARIAGO, CLOQUIN, (LARIAGO, CLOQUIN, NIVAQUINE P)NIVAQUINE P)

Oral - 10 mg/kg stat and 5 Oral - 10 mg/kg stat and 5 mg/kg * 3 doses over next mg/kg * 3 doses over next 48 hours 48 hours

IM Not recommendedIM Not recommended

DoC for P Vivax DoC for P Vivax (uncomplicated)(uncomplicated)

QuinineQuinine

(300/600mg Base tab,(300/600mg Base tab,

300mg/ml Inj)300mg/ml Inj)(CINKONA, KWINIL, (CINKONA, KWINIL, QUININE)QUININE)

Oral - 10 mg/kg 8 hourly Oral - 10 mg/kg 8 hourly for 4 days and 5 mg/kg 8 for 4 days and 5 mg/kg 8 hourly for 3 days. hourly for 3 days. IV - 16 mg of base/kg in 10 IV - 16 mg of base/kg in 10 ml/kg NS/5% dextrose over ml/kg NS/5% dextrose over 4 hours, then 8 mg of 4 hours, then 8 mg of salt/kg over 4 hours, every salt/kg over 4 hours, every 8 hours for 5-7 days. 8 hours for 5-7 days.

DoC for P Falciparum DoC for P Falciparum

Oral – UncomplicatedOral – Uncomplicated

IV – Complicated/ Cerebral IV – Complicated/ Cerebral MalariaMalaria

MefloquineMefloquine

(250mg base Tablet) (250mg base Tablet)

(LARIMEF, MEFLOTAS, (LARIMEF, MEFLOTAS, MEFLOC, MQF)MEFLOC, MQF)

25 mg/kg in 1-2 divided 25 mg/kg in 1-2 divided dosedose

Avoid in seizures, cardiac Avoid in seizures, cardiac disease. disease. Do NOT use with Quinine.Do NOT use with Quinine.

Do NOT re-treat with Do NOT re-treat with MefloquineMefloquine

Sulphadoxime/ Sulphadoxime/ Pyrimethamine (S/P)Pyrimethamine (S/P)

(500 mg / 25 mg)(500 mg / 25 mg)

(LARIDOX, PYRALFIN, (LARIDOX, PYRALFIN, METAKELFIN, REZIZ)METAKELFIN, REZIZ)

Oral – 1.25 mg /kg of Oral – 1.25 mg /kg of PyrimethaminePyrimethamine

Avoid in Sulfa allergyAvoid in Sulfa allergy

Add-on therapy for CQR Add-on therapy for CQR malaria (never alone)malaria (never alone)

PrimaquinePrimaquine

tablets containing 2.5, 7.5 tablets containing 2.5, 7.5 and 15 mg and 15 mg

(PMQ-INGA)(PMQ-INGA)

Oral - 0.25mg/kg/day (once Oral - 0.25mg/kg/day (once a day) for 14 days in P. a day) for 14 days in P. vivax; 0.75 mg/kg as single vivax; 0.75 mg/kg as single dose in P. falciparum dose in P. falciparum

Avoid with Quinine/ Avoid with Quinine/ Mefloquine, in severe Mefloquine, in severe G6PD Deficient pt.G6PD Deficient pt.

To be used in ALL cases of To be used in ALL cases of MalariaMalaria

Other drugs include Tetracyclines, Proguanil, Halofantrine, Lumefantrine, Mepacrine, Other drugs include Tetracyclines, Proguanil, Halofantrine, Lumefantrine, Mepacrine, Bulaquine, clindamycin etc.Bulaquine, clindamycin etc.

ArtesunateArtesunate(60 mg/ml Inj, 50 mg (60 mg/ml Inj, 50 mg tablet)tablet)

(FALCIGO, (FALCIGO, FALCIQUIN, FALCIQUIN, FALCICARE, FALCICARE, ARTISIN)ARTISIN)

IM/IV 2.4 mg/kg LD, IM/IV 2.4 mg/kg LD, followed by 1.2 mg/kg followed by 1.2 mg/kg for 7 daysfor 7 days

Oral- 4 mg/kg on the Oral- 4 mg/kg on the first day followed by first day followed by 2mg/kg for 6 days2mg/kg for 6 days

Recommended for Recommended for Severe Falciparum Severe Falciparum Malaria, as combination Malaria, as combination therapytherapy

ArteetherArteether

(150mg/ 2ml Inj, 50 mg (150mg/ 2ml Inj, 50 mg tablet)tablet)

(FALCIGUARD, (FALCIGUARD, RAPITHER, MALIJET, RAPITHER, MALIJET, ARTISUN)ARTISUN)

3 mg/kg OD for 3 days3 mg/kg OD for 3 days Well toleratedWell tolerated

Artemether Artemether

(80 mg/ml Inj. and 40 (80 mg/ml Inj. and 40 mg cap)mg cap)(LARITHER, (LARITHER, MALITHER)MALITHER)

3.2mg/kg as loading 3.2mg/kg as loading dose, followed by dose, followed by 1.6mg/kg daily, until 1.6mg/kg daily, until patient is able to patient is able to swallow or for 5 days. swallow or for 5 days.

May cause LFTs rise.May cause LFTs rise.

Antimalarial drugs – ACT Antimalarial drugs – ACT Artemisinin based combination therapy (ACT) Artemisinin based combination therapy (ACT)

Increase cure rates, Increase cure rates, reduce the development of resistance. reduce the development of resistance.

Disadvantages of ACT Disadvantages of ACT High costHigh cost Increased side effectsIncreased side effects Pharmacokinetic mismatchPharmacokinetic mismatch

Artesunate + Sulfadoxine/Pyrimethamine (SP)Artesunate + Sulfadoxine/Pyrimethamine (SP)Artesunate 4mg/kg once daily for 3 days Artesunate 4mg/kg once daily for 3 days and SP single dose of 25mg/kg and 1.25mg/kg respectively and SP single dose of 25mg/kg and 1.25mg/kg respectively

ArtesunateArtesunate (as above) + (as above) + MefloquineMefloquine 8mg/kg daily for three days 8mg/kg daily for three days Artemether + Lumefantrine, Artemether + Lumefantrine, Artesunate + Doxy, Artesunate + ClindaArtesunate + Doxy, Artesunate + Clinda

Treatment protocolTreatment protocol

P Vivax – ChloroquineP Vivax – Chloroquine+ Primaquine for 14 days + Primaquine for 14 days

P Falciparum - Treat depending on severity & P Falciparum - Treat depending on severity & sensitivity, sensitivity, Use Quinine Or ACTUse Quinine Or ACT

+ Primaquine single dose for gametocidal activity.+ Primaquine single dose for gametocidal activity. Severe Malaria/ Cerebral Malaria – Always treat with Severe Malaria/ Cerebral Malaria – Always treat with

IV drugsIV drugs Quinine / Artemisinin + Tetra/ Clinda till accepting orally Quinine / Artemisinin + Tetra/ Clinda till accepting orally

and then switch to oral medicinesand then switch to oral medicines

TreatmentTreatment Pregnancy – Quinine in all trimesters; Artemesinin in 2Pregnancy – Quinine in all trimesters; Artemesinin in 2ndnd and and

33rdrd trimesters trimesters For For P. falciparumP. falciparum malaria, follow-up MP tests on 6th and 28th malaria, follow-up MP tests on 6th and 28th

days after treatment. days after treatment. The 6th day smear is done to assess clearance of parasitemiaThe 6th day smear is done to assess clearance of parasitemia 28th day smear is done to identify recrudescence. 28th day smear is done to identify recrudescence.

Failure after 6Failure after 6thth day – resistance – treat with second line drugs day – resistance – treat with second line drugs (Art + Tetra / Clinda; Quinine + Tetra / Clinda)(Art + Tetra / Clinda; Quinine + Tetra / Clinda)

Failure after 28 days – new infection/ recrudescence – treat Failure after 28 days – new infection/ recrudescence – treat with first line drugs againwith first line drugs again

Relapse – after months – mostly due to Primaquine not given Relapse – after months – mostly due to Primaquine not given in P vivax – treat with first line drugsin P vivax – treat with first line drugs

Important PointsImportant Points

Oral medicines NOT to be used in Oral medicines NOT to be used in severe Falciparum Malariasevere Falciparum Malaria

It takes 48 hours for fever to It takes 48 hours for fever to subsidesubside

Do not administer extra dose, do Do not administer extra dose, do not change medicine and avoid not change medicine and avoid using newer drugs to reduce drug using newer drugs to reduce drug resistanceresistance

Give Primaquine in all cases.Give Primaquine in all cases.

Indications for hospitalization of Indications for hospitalization of malarial casesmalarial cases

Persistence of fever even after 48 hours of Persistence of fever even after 48 hours of initial treatment. initial treatment.

Continuously worsening headache. Continuously worsening headache. Persistent vomiting. Persistent vomiting. Any complications of Any complications of P. P. falciparumfalciparum malaria malaria- -

altered sensorium, convulsions, anemia, altered sensorium, convulsions, anemia, jaundice, hyperpyrexia, bleeding and jaundice, hyperpyrexia, bleeding and clotting disorders, breathlessness, high clotting disorders, breathlessness, high coloured urine etc. coloured urine etc.

Patients who are at higher risk for development of complications of for development of complications of P. P. falciparumfalciparum malaria-extremes of age, pregnancy etc. malaria-extremes of age, pregnancy etc. Patients who appear sick and prostrated Patients who appear sick and prostrated Significant dehydrationSignificant dehydration

Preventing MalariaPreventing MalariaPersonal protectionPersonal protection Preventing the mosquitoes from Preventing the mosquitoes from

entering the house – Close door / entering the house – Close door / windows, especially toilets. Well-windows, especially toilets. Well-constructed houses with window constructed houses with window screensscreens

Preventing the mosquitoes from Preventing the mosquitoes from hiding – Avoid dark corners/ hanging hiding – Avoid dark corners/ hanging clothes in roomsclothes in rooms

Mosquito Control – Avoid stagnant Mosquito Control – Avoid stagnant water, insecticide spraying etc.water, insecticide spraying etc.

Preventing MalariaPreventing Malaria

Protection from mosquito bites – Protection from mosquito bites – Protective clothing, Protective clothing, Mosquito repellants (containing DEET),Mosquito repellants (containing DEET), Insect vaporizers (coils & mats containing Insect vaporizers (coils & mats containing

pyrethroids), pyrethroids), Insecticide treated bed nets (most Insecticide treated bed nets (most effective),effective),AirconditioningAirconditioning

Chemoprophylaxis - IndiaChemoprophylaxis - India

AREA 1 -Jammu and Kashmir, Himachal Pradesh AREA 1 -Jammu and Kashmir, Himachal Pradesh and Sikkim – No risk – No Prophylaxisand Sikkim – No risk – No Prophylaxis

AREA 2 – North East States (High Risk, High AREA 2 – North East States (High Risk, High Incidence of CQ resistance) – MEFLOQUINEIncidence of CQ resistance) – MEFLOQUINE

AREA 3 – Rest of India (Medium risk, Intermediate AREA 3 – Rest of India (Medium risk, Intermediate CQ resistance) – CQ + PGCQ resistance) – CQ + PG

CQ alone is NOT recommended in INDIA for CQ alone is NOT recommended in INDIA for prophylaxisprophylaxis

Other drugs that maybe used for prophylaxis include Doxycycline & Other drugs that maybe used for prophylaxis include Doxycycline & Malarone (Atovaquone + Proguanil)Malarone (Atovaquone + Proguanil)

ChloroquineChloroquine(150 mg Base/ Tablet(150 mg Base/ TabletSyp 50 mg/ 5ml Base)Syp 50 mg/ 5ml Base)

300 mg Once weekly300 mg Once weekly5 mg/kg weekly5 mg/kg weekly

Start one week before Start one week before exposure, continue exposure, continue during exposure and for during exposure and for 4 weeks thereafter 4 weeks thereafter

ProguanilProguanil 200 mg Daily200 mg Daily< 2yr – 50 mg / day< 2yr – 50 mg / day2-6 yr – 100 mg/day2-6 yr – 100 mg/day

7-9 yr – 150 mg/day7-9 yr – 150 mg/day

> 9 yr – 200 mg/day> 9 yr – 200 mg/day

Start 1-2 days before, Start 1-2 days before, continue during continue during exposure and for 4 exposure and for 4 weeks thereafter weeks thereafter

MefloquineMefloquine

((Tablet with 250mg ((Tablet with 250mg base, 274mg salt) base, 274mg salt)

250 mg base once 250 mg base once weeklyweekly

5mg/kg once weekly5mg/kg once weekly

Start 2-3 weeks before, Start 2-3 weeks before, continue during continue during exposure and for 4 exposure and for 4 weeks thereafterweeks thereafter

Malaria Vaccine – Why is it so Malaria Vaccine – Why is it so difficult?difficult?

Researchers must identify which of the Researchers must identify which of the Plasmodium parasite's 5,300 proteins provoke Plasmodium parasite's 5,300 proteins provoke a strong immune response.a strong immune response.

Parasite makes different proteins at each stage Parasite makes different proteins at each stage of its lifecycle. of its lifecycle.

Over two decades, research and hundreds of Over two decades, research and hundreds of millions of dollars have been invested in millions of dollars have been invested in developing a vaccine for malaria. developing a vaccine for malaria.

Malaria - VaccineMalaria - VaccineThe RTS,S vaccine has been more than two decades in the The RTS,S vaccine has been more than two decades in the

making and more than US $400 million has been invested in making and more than US $400 million has been invested in the project. the project.

On 26th May 2009 On 26th May 2009 phase III trials of the phase III trials of the world's most advanced world's most advanced candidate vaccine have candidate vaccine have started. started. 16,000 children aged 16,000 children aged two and under will two and under will receive the vaccine receive the vaccine over the coming over the coming months. months.

If all goes well If all goes well (above 50 % (above 50 % protection) it will protection) it will be in the market by be in the market by 2012.2012.