chemotherapy and national drug policy in malaria

Dr.G.C Sahu/ROHFW/GoI/A'Bad 1

CHEMOTHERAPY AND NATIONAL DRUG POLICY IN CHEMOTHERAPY AND NATIONAL DRUG POLICY IN MALARIA.MALARIA.

DR .G . C. SAHUROH&FW; GoI;AHMEDABAD

DR .G . C. SAHUDR .G . C. SAHUROH&FW; ROH&FW; GoIGoI;;AHMEDABADAHMEDABAD


SEQUENCE OF

EVENTS…

SEQUENCE SEQUENCE OF OF

EVENTSEVENTS……

…. IN THE LIFE CYCLE

OF MALARIA PARASITE

……. IN THE . IN THE LIFE CYCLE LIFE CYCLE

OF MALARIA OF MALARIA PARASITEPARASITE

Infective vector mosq.bite Sporozoite inoculation Liver cycle

Repeatative RBC cycleVec.mosq.picks up Gametocytes

Mosquito cycle


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An effective treatment policy should aim to:

Reduce morbidity

Prevent the progression of uncomplicated disease into severe and potentially fatal disease and thereby reduce malaria mortality

Reduce the impact of placental malaria infection and maternal malaria-associated anaemia through chemoprophylaxis or preventive intermittent therapy.

Prevent or delay the development of antimalarialdrug resistance by correct diagnosis and rational treatment of all malaria positive cases.

An effective treatment policy should aim to:An effective treatment policy should aim to:

Reduce morbidityReduce morbidity

Prevent the progression of uncomplicated disease Prevent the progression of uncomplicated disease into severe and potentially fatal disease and thereby into severe and potentially fatal disease and thereby reduce malaria mortalityreduce malaria mortality

Reduce the impact of placental malaria infection Reduce the impact of placental malaria infection and maternal malariaand maternal malaria--associated associated anaemiaanaemia through through chemoprophylaxis or preventive intermittent therapy.chemoprophylaxis or preventive intermittent therapy.

Prevent or delay the development of Prevent or delay the development of antimalarialantimalarialdrug resistance by correct diagnosis and rational drug resistance by correct diagnosis and rational treatment of all malaria positive cases.treatment of all malaria positive cases.

AimsAims CausationCausation TherapyTherapy DrugsDrugs

To alleviate To alleviate symptomssymptoms

Symptoms are Symptoms are caused by blood caused by blood

forms of the forms of the parasiteparasite

Blood Blood schizonticidalschizonticidal

drugsdrugs

ChloroquineChloroquine, , quinine, quinine,

pyrimethamine/spyrimethamine/sulphadoxineulphadoxine, , artemisininartemisinin

To prevent To prevent relapsesrelapses

Relapses are due Relapses are due to to hypnozoiteshypnozoites of of P. P. vivaxvivax/ P. / P. ovaleovale

Tissue Tissue schizonticidalschizonticidal

drugsdrugsPrimaquinePrimaquine

To prevent spreadTo prevent spread Spread is through Spread is through the gametocytesthe gametocytes

GametocytocidalGametocytocidaldrugsdrugs

PrimaquinePrimaquine for P. for P. falciparumfalciparum, ,

ChloroquineChloroquine for for all otherall other

Thus, in effect, a blood schizonticidal drug and primaquine should be administered to ALL types of malaria.

Thus, in effect, a blood Thus, in effect, a blood schizonticidalschizonticidal drug and drug and primaquineprimaquine should be should be administered to ALL types of malaria.administered to ALL types of malaria.

Treatment of Malaria Treatment of Malaria ------ Aims Of TreatmentAims Of Treatment

Principles Of TreatmentPrinciples Of TreatmentPrinciples Of Treatment

Treatment of malaria depends on the following factors:

Type of infection. Severity of infection. Status of the host. Associated conditions/ diseases.

Treatment of malaria depends on the following factors:Treatment of malaria depends on the following factors:

Type of infection. Type of infection. Severity of infection. Severity of infection. Status of the host. Status of the host. Associated conditions/ diseases. Associated conditions/ diseases.

Associated conditions/ diseases: Associated conditions/ diseases: Associated conditions/ diseases: Treatment of malaria may have to be modified due to certain associated conditions/ diseases.

Therefore, all such should be carefully assessed before starting the patient on anti malarial treatment.

Treatment of malaria may have to be modified due to certain assoTreatment of malaria may have to be modified due to certain associated conditions/ diseases. ciated conditions/ diseases. Therefore, all such should be carefully assessed before startingTherefore, all such should be carefully assessed before starting the patient on anti malarial the patient on anti malarial

treatment. treatment.

Pregnancy: Treatment of malaria in pregnancy may prove to be difficult due to contra indication for use of certain antimalarials. Chloroquine can be used safely in all trimesters of pregnancy. Artemisinin is not shown to have any deleterious effects on the fetus in animal studies and therefore can be considered if the situation demands. Quinine can be used in pregnancy, but one should be watchful about hypoglycemia.

Epilepsy: Malaria as well as anti malarials can trigger convulsions. Mefloquine is better avoided in these patients.

Cardiac disease: High-grade fever of malaria can exacerbate left ventricular failure and therefore, in all such patients energetic management of malaria is called for. Fever should be controlled with anti-pyretics and tepid sponging. Chloroquine, artemisinin, pyrimethamine/ sulphadoxine, tetracyclines and primaquine can be safely used in these patients. Quinine can also be used carefully. Mefloquine and halofantrine are better avoided in patients with known cardiac illness.

Hepatic insufficiency: None of the antimalarial drugs have any direct hepatotoxic effect. However, chloroquine is not advisable in patients with severe hepatic insufficiency.

Renal failure: The initial dose of antimalarial drugs need not be reduced in patients with renal failure. However, if the patient requires parenteral antimalarials even after three days and continues to be sick, then the dose can be reduced by one third to half of usual dose.

Dermatitis: Concomitant use of chloroquine with gold salts and phenyl butazone should be avoided because all the three can cause dermatitis.

Pregnancy:Pregnancy: Treatment of malaria in pregnancy may prove to be difficult dueTreatment of malaria in pregnancy may prove to be difficult due to contra indication for use of certain to contra indication for use of certain antimalarialsantimalarials. . ChloroquineChloroquine can be used safely in all trimesters of pregnancy. can be used safely in all trimesters of pregnancy. ArtemisininArtemisinin is not shown to have any is not shown to have any deleterious effects on the fetus in animal studies and thereforedeleterious effects on the fetus in animal studies and therefore can be considered if the situation demands. Quinine can be considered if the situation demands. Quinine can be used in pregnancy, but one should be watchful about hypogcan be used in pregnancy, but one should be watchful about hypoglycemia. lycemia.

Epilepsy:Epilepsy: Malaria as well as anti Malaria as well as anti malarialsmalarials can trigger convulsions. can trigger convulsions. MefloquineMefloquine is better avoided in these patients. is better avoided in these patients.

Cardiac diseaseCardiac disease:: HighHigh--grade fever of malaria can exacerbate left ventricular failure agrade fever of malaria can exacerbate left ventricular failure and therefore, in all such nd therefore, in all such patients energetic management of malaria is called for. Fever shpatients energetic management of malaria is called for. Fever should be controlled with antiould be controlled with anti--pyreticspyretics and tepid and tepid sponging. sponging. ChloroquineChloroquine, , artemisininartemisinin, , pyrimethaminepyrimethamine/ / sulphadoxinesulphadoxine, , tetracyclinestetracyclines and and primaquineprimaquine can be safely used in can be safely used in these patients. Quinine can also be used carefully. these patients. Quinine can also be used carefully. MefloquineMefloquine and and halofantrinehalofantrine are better avoided in patients with are better avoided in patients with known cardiac illness. known cardiac illness.

Hepatic insufficiencyHepatic insufficiency:: None of the None of the antimalarialantimalarial drugs have any direct drugs have any direct hepatotoxichepatotoxic effect. However, effect. However, chloroquinechloroquine is not advisable in patients with severe hepatic insufficiency.is not advisable in patients with severe hepatic insufficiency.

Renal failure:Renal failure: The initial dose of The initial dose of antimalarialantimalarial drugs need not be reduced in patients with renal failure. Howevdrugs need not be reduced in patients with renal failure. However, if er, if the patient requires the patient requires parenteralparenteral antimalarialsantimalarials even after three days and continues to be sick, then the dose ceven after three days and continues to be sick, then the dose can be an be reduced by one third to half of usual dose.reduced by one third to half of usual dose.

Dermatitis:Dermatitis: Concomitant use of Concomitant use of chloroquinechloroquine with gold salts and phenyl with gold salts and phenyl butazonebutazone should be avoided because all should be avoided because all the three can cause dermatitis. the three can cause dermatitis.

Anti-malarials contra-indicated in pregnancy.

× Mefloquine:- 1st trimester

× S-P combination:- 1st and last trimester

× Halo,Tetra,Doxy:- All trimester

× Primaquine:- All trimester.

AntiAnti--malarialsmalarials contracontra--indicated in pregnancy.indicated in pregnancy.

×× MefloquineMefloquine::-- 11stst trimestertrimester

×× SS--P combination:P combination:-- 11stst and last trimesterand last trimester

×× Halo,Tetra,DoxyHalo,Tetra,Doxy::-- All trimesterAll trimester

×× PrimaquinePrimaquine::-- All trimester.All trimester.

In an endemic area, malaria often presents with atypical manifestationsIn an endemic area, malaria often presents with In an endemic area, malaria often presents with atypicalatypical manifestationsmanifestations

Atypical features are more common in the following situations:

Falciparum malaria

Early infection

Patients at extremes of age

Patients who are immune-compromised (extremes of age, malnourished, AIDS, tuberculosis, cancers, on immunosuppressive therapy etc.)

Patients on chemoprophylaxis for malaria

Patients who have had recurrent attacks of malaria

Patients with end stage organ failure

Last but not the least, pregnancy.

Atypical features are more common in the following situations:Atypical features are more common in the following situations:

FalciparumFalciparum malaria malaria

Early infection Early infection

Patients at extremes of age Patients at extremes of age

Patients who are immunePatients who are immune--compromised (extremes of age, malnourished, AIDS, compromised (extremes of age, malnourished, AIDS, tuberculosis, cancers, on immunosuppressive therapy etc.) tuberculosis, cancers, on immunosuppressive therapy etc.)

Patients on chemoprophylaxis for malaria Patients on chemoprophylaxis for malaria

Patients who have had recurrent attacks of malaria Patients who have had recurrent attacks of malaria

Patients with end stage organ failure Patients with end stage organ failure

Last but not the least, pregnancy. Last but not the least, pregnancy.


INFORMATIONS ONE MUST HAVE BEFORE TREATING ACASE OF MALARIA.

INFORMATIONS ONE MUST HAVE BEFORE TREATING AINFORMATIONS ONE MUST HAVE BEFORE TREATING ACASE OF MALARIA.CASE OF MALARIA.

THE TYPE OF SPECIES YOU ARE TREATING i eTHE TYPE OF SPECIES YOU ARE TREATING i eP. VIVAX OR P. FALCIPARUMP. VIVAX OR P. FALCIPARUM

THE STAGE OF PARASITES YOU ARE TREATING THE STAGE OF PARASITES YOU ARE TREATING i.ei.eASEXUAL STAGE(RING) OR SEXUAL STAGE(GAMETO) ASEXUAL STAGE(RING) OR SEXUAL STAGE(GAMETO)

THE TYPE OF TREATEMENT YOU ARE GIVING THE TYPE OF TREATEMENT YOU ARE GIVING i.ei.e{{PRESUMPTIVE TREATMENT OR RADICAL TREATMENT}PRESUMPTIVE TREATMENT OR RADICAL TREATMENT}Type of severity of infection Type of severity of infection i.ei.e complicated or non complicated.complicated or non complicated.

THE TYPE OF AREA IN WHICH THE TREATMENT IS THE TYPE OF AREA IN WHICH THE TREATMENT IS GIVEN i.e. GIVEN i.e. LOWLOW--RISK AREA OR HIGH RISK AREARISK AREA OR HIGH RISK AREA..

RESPONSE OF THE PARASITE TO THE DRUG GIVEN RESPONSE OF THE PARASITE TO THE DRUG GIVEN i.e. i.e. SENSITIVE OR RESISTANTSENSITIVE OR RESISTANT..


SCHIZONTICIDAL DRUGS:SCHIZONTICIDAL DRUGS:CHLOROQUINE, AMODIAQUINE, QUININE, CHLOROQUINE, AMODIAQUINE, QUININE,

QUINIDINE,PYREMETHAMINE, TRIMETHOPRIM, QUINIDINE,PYREMETHAMINE, TRIMETHOPRIM, PROGUANIL, SULFONAMIDES IN COMBN. PROGUANIL, SULFONAMIDES IN COMBN. WITHPYREMETHAMINE, MEFLOQUINE, HALOFANTRINE, WITHPYREMETHAMINE, MEFLOQUINE, HALOFANTRINE, ARTEMESININEARTEMESININE..


GAMETOCIDAL AND ANTIGAMETOCIDAL AND ANTI--RELAPSE DRUG(S) :RELAPSE DRUG(S) :

PRIMAQUINEPRIMAQUINE

What would be the optimal anti-malaria compound?(1)

The optimal anti-malaria compound must have such six advantages therapeutically as follows:

• High efficacy The 28-day cure rate should be over 95% in multi-drugs resistant falciparum malaria endemic areas

• Quick acting The development of parasites should be stopped after the initial dose, which is the key point to reduce the incidence of cerebral malaria , thereby, reduced the mortality of malaria

Dr.G.C Sahu/ROHFW/GoI/A'Bad


• Short treatment course The optimal treatment course with better patients' compliance would be once daily for just two days.

• Low toxicity The incidence of side effects should be less than 5%.


• Preventing transmission It will be advantages to control the prevalence of malaria and very important for preventing from the disease to neutralize and kill quickly the gametocytes of falciparummalaria

• Low cost It should be affordable for most of the patients in malaria endemic areas of the developing countries, so that those patients could take the drug to cure malaria.


Anti Malarial Drugs: Anti Malarial Drugs: ChloroquineChloroquine

Mechanism of action: Mechanism of action:

The mechanism of action of The mechanism of action of chloroquinechloroquine is unclear. Being is unclear. Being alkaline, the drug reaches high concentration within the food alkaline, the drug reaches high concentration within the food vacuoles of the parasite and raises its pH. It is found to vacuoles of the parasite and raises its pH. It is found to induce rapid clumping of the pigment. induce rapid clumping of the pigment. ChloroquineChloroquine inhibits inhibits the parasitic enzyme the parasitic enzyme hemeheme polymerasepolymerase that converts the that converts the toxic toxic hemeheme into noninto non--toxic toxic hemazoinhemazoin, thereby resulting in the , thereby resulting in the accumulation of toxic accumulation of toxic hemeheme within the parasite.within the parasite. It may also It may also interfere with the biosynthesis of nucleic acids. Other interfere with the biosynthesis of nucleic acids. Other mechanisms suggested include formation of drugmechanisms suggested include formation of drug--hemehemecomplex, intercalation of the drug with the parasitic DNA etc.complex, intercalation of the drug with the parasitic DNA etc.


Anti Malarial Drugs: Quinine

Mechanism of action:

Quinine acts as a blood schizonticide although it also has gametocytocidalactivity against P. vivax and P. malariae. Because it is a weak base, it is concentrated in the food vacuoles of P. falciparum. It is said to act by inhibiting heme polymerase, thereby allowing accumulation of its cytotoxic substrate, heme. As a schizonticidal drug, it is less effective and more toxic than chloroquine. However, it has a special place in the management of severe falciparum malaria in areas with known resistance to chloroquine.

Food Food VacuoVacuo

lele

HemeHemepolymepolyme

raserase

HemoHemoglobinglobin

Toxic Toxic HemeHeme

Non Toxic Non Toxic HemazoinHemazoin(Malarial (Malarial PigmentPigment))

DegradatDegradationion

? Inhibited ? Inhibited by Quinineby Quinine


Pyrimethamine and sulphadoxine are very useful adjuncts in the treatment of uncomplicated, chloroquine resistant, P. falciparum malaria.

Anti malarial activity:

Pyrimethamine inhibits the dihydrofolate reductase of plasmodia and thereby blocks the biosynthesis of purines and pyrimidines, which are so essential for DNA synthesis and cell multiplication. This leads to failure of nuclear division at the time of schizont formation in erythrocytes and liver.Availability: Pyrimethamine and sulphadoxine combined tablets are available, containing 25 mg of pyrimethamine and 500 mg of sulphadoxinein each tablet.

Dose of Pyrimethamine/sulfadoxine:3 tablets as per the WHO recommendations

PyrimethaminePyrimethamine and and sulphadoxinesulphadoxine are very useful adjuncts in the treatment are very useful adjuncts in the treatment of uncomplicated, of uncomplicated, chloroquinechloroquine resistant, P. resistant, P. falciparumfalciparum malaria. malaria.

Anti malarial activity: Anti malarial activity:

PyrimethaminePyrimethamine inhibits the inhibits the dihydrofolatedihydrofolate reductasereductase of plasmodiaof plasmodia and and thereby blocks the biosynthesis of thereby blocks the biosynthesis of purinespurines and and pyrimidinespyrimidines, which are so , which are so essential for DNA synthesis and cell multiplication. This leads essential for DNA synthesis and cell multiplication. This leads to failure of to failure of nuclear division at the time of nuclear division at the time of schizontschizont formation in erythrocytes and liver.formation in erythrocytes and liver.Availability: Availability: PyrimethaminePyrimethamine and and sulphadoxinesulphadoxine combined tablets are combined tablets are available, containing 25 mg of available, containing 25 mg of pyrimethaminepyrimethamine and 500 mg of and 500 mg of sulphadoxinesulphadoxinein each tablet.in each tablet.

Dose of Dose of Pyrimethamine/sulfadoxinePyrimethamine/sulfadoxine::3 tablets as per the WHO recommendations3 tablets as per the WHO recommendations

Anti Malarial Drugs: Pyrimethamine/ SulphadoxineAnti Malarial Drugs: Pyrimethamine/ Sulphadoxine


Anti Malarial Drugs:MefloquineAnti Malarial Drugs:Mefloquine

Mefloquine was born during the Vietnam war, as a result of research into newer anti malarials, to protect the American soldiers from the multi drug resistant falciparum malaria. Nothing much has happened after that and

hence this 'new' drug should be restricted for use against multi drug resistant falciparum only.

Anti malarial activity:

Mefloquine has been found to produce swelling of the P. falciparum food vacuoles. It may act by forming toxic complexes with free heme that damage membranes and interact with other plasmodial components. It is effective against the blood forms of falciparum malaria, including the chloroquineresistant types.

Availability: It is available as 250 mg tablets.Dose: 15 mg/kg in a single dose. If the dose exceeds 1000 mg, the second dose can be given after 4-8 hours to minimise gastric irritation. Total dose should

not exceed 1500 mg.

MefloquineMefloquine was born during the Vietnam war, as a result of research into was born during the Vietnam war, as a result of research into newer anti newer anti malarialsmalarials, to protect the American soldiers from the multi drug , to protect the American soldiers from the multi drug resistant resistant falciparumfalciparum malaria. Nothing much has happened after that and malaria. Nothing much has happened after that and

hence this 'new' drug should be restricted for use against multihence this 'new' drug should be restricted for use against multi drug drug resistant resistant falciparumfalciparum only.only.

Anti malarial activity:Anti malarial activity:

MefloquineMefloquine has been found to produce swelling of the P. has been found to produce swelling of the P. falciparumfalciparum food food vacuoles. It may act by forming toxic complexes with free vacuoles. It may act by forming toxic complexes with free hemeheme that damage that damage membranes and interact with other membranes and interact with other plasmodialplasmodial components. It is effective components. It is effective against the blood forms of against the blood forms of falciparumfalciparum malaria, including the malaria, including the chloroquinechloroquineresistant types.resistant types.

Availability: It is available as 250 mg tablets.Availability: It is available as 250 mg tablets.Dose: 15 mg/kg in a single dose. If the dose exceeds 1000 mg, thDose: 15 mg/kg in a single dose. If the dose exceeds 1000 mg, the second dose e second dose can be given after 4can be given after 4--8 hours to 8 hours to minimiseminimise gastric irritation. Total dose should gastric irritation. Total dose should

not exceed 1500 mg. not exceed 1500 mg.

Artemesia annuaSweet Annie

Sweet wormwood Annual wormwood

Qinghao

ArtemesiaArtemesia annuaannua

Sweet Annie Sweet Annie Sweet wormwood Sweet wormwood

Annual wormwood Annual wormwood QinghaoQinghao



Anti Malarial Drugs:Anti Malarial Drugs:

It is the fastest acting anti malarial available. It inhibits the development of the trophozoites and thus prevents progression of the disease. It starts acting within 12 hours. It is also effective against the chloroquine resistant strains of P. falciparum. These properties of the drug are very useful in managing complicated P. falciparummalaria.

Dose:Artemether: 3.2 mg/kg intra muscularly as a loading dose, followed by 1.6 mg/kg

daily until oral therapy or a maximum of 7 days.Arteether: 3 mg/kg once a day for 3 days, as deep intra muscular injection.

Artesunate: Oral- 5 mg/kg on the first day followed by 2.5 mg/kg on the second and third days. Oral artesunate is not recommended in pregnancy.

Parenteral- Loading dose of 2.4 mg/kg followed by 1mg/kg after 4 hours and 24 hours; thereafter, 1.2 mg/kg daily for maximum of 7 days. For children, the recommended

dose is 1.2 mg/kg/day for 5-7 days.

It is the fastest acting anti malarial available. It inhibits the development of the trophozoites and thus prevents progression of the disease. It starts acting within 12 hours. It is also effective against the chloroquine resistant strains of P. falciparum. These properties of the drug are very useful in managing complicated P. falciparummalaria.

Dose:Artemether: 3.2 mg/kg intra muscularly as a loading dose, followed by 1.6 mg/kg

daily until oral therapy or a maximum of 7 days.Arteether: 3 mg/kg once a day for 3 days, as deep intra muscular injection.

Artesunate: Oral- 5 mg/kg on the first day followed by 2.5 mg/kg on the second and third days. Oral artesunate is not recommended in pregnancy.

Parenteral- Loading dose of 2.4 mg/kg followed by 1mg/kg after 4 hours and 24 hours; thereafter, 1.2 mg/kg daily for maximum of 7 days. For children, the recommended

dose is 1.2 mg/kg/day for 5-7 days.

Anti Malarial Drugs: The Artemisinin DerivativesAnti Malarial Drugs: The Artemisinin Derivatives

Site of ActionSite of ActionSite of Action

ArtemisininArtemisininArtemisinin

ArtemisininArtemisininArtemisinin

Conventional TreatmentConventional Conventional TreatmentTreatment


ArtemisininsArtemisinins



Anti Malaria Drugs: PrimaquineAnti Malaria Drugs: Primaquine

Primaquine is the essential co-drug with chloroquine in treating all cases of malaria. It is highly effective against the gametocytes of all plasmodia and thereby prevents spread of the disease to the mosquito from the patient. It is also effective against the dormant tissue forms of P. vivax and P. ovale malaria, and thereby offers radical cure and prevents relapses. It has insignificant activity against the asexual blood forms of the parasite and therefore it is always used in conjunction with a blood schizonticide and never as a single agent.

Mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by interfering with the electron transport in the parasite.

Availability: Primaquine is available as tablets containing 2.5, 7.5 and 15 mg of the salt.

PrimaquinePrimaquine is the essential cois the essential co--drug with drug with chloroquinechloroquine in treating all in treating all cases of malaria. It is highly effective against the gametocytescases of malaria. It is highly effective against the gametocytes of all of all plasmodia and thereby prevents spread of the disease to the mosqplasmodia and thereby prevents spread of the disease to the mosquito uito from the patient. It is also effective against the dormant tissufrom the patient. It is also effective against the dormant tissue forms of e forms of P. P. vivaxvivax and and P. P. ovaleovale malaria, and thereby offers radical cure and malaria, and thereby offers radical cure and prevents relapses. It has insignificant activity against the aseprevents relapses. It has insignificant activity against the asexual blood xual blood forms of the parasite and therefore it is always used in conjuncforms of the parasite and therefore it is always used in conjunction tion with a blood with a blood schizonticideschizonticide and never as a single agent. and never as a single agent.

Mechanism of action is not well understood. It may be acting by Mechanism of action is not well understood. It may be acting by generating reactive oxygen species or by generating reactive oxygen species or by interfering with the interfering with the electron transport in the parasite.electron transport in the parasite.

Availability: Availability: PrimaquinePrimaquine is available as tablets containing 2.5, 7.5 and is available as tablets containing 2.5, 7.5 and 15 mg of the salt.15 mg of the salt.


Drug Drug ClassClass

Drugs Drugs

Blood Blood SchizontoSchizonto

cidalcidal

ChloroquineChloroquine, Quinine, , Quinine, QuinidineQuinidine, , MefloquineMefloquine, , HalofantrineHalofantrine, Sulfonamides, , Sulfonamides, TetracyclinesTetracyclines, ,

AtovaquoneAtovaquone, , ArtemisininArtemisinin compounds compounds

Tissue Tissue SchizontoSchizonto

cidalcidal

PrimaquinePrimaquine, , ProguanilProguanil, , PyrimethaminePyrimethamine, ,

GametocidalGametocidal PrimaquinePrimaquine

HypnozoitHypnozoitocidalocidal

PrimaquinePrimaquine


What is presumptive treatment? **Presumption - In an area with high transmission of malaria, it should be presumed that ALL cases of fever are due to malaria.Treatment - First loading dose of chloroquine should be administered immediately after collecting the blood specimen, even without waiting for its report.

If the fever is indeed malaria, this treatment alleviates symptoms early, may be well before the test result is available.

If it is malaria, chloroquine also prevents the spread of malaria by destroying the gametocytes of P. vivax (the more common malaria).

If it is not malaria, nothing is lost, for chloroquine at this dose is safe and has no adverse effects.

It cures early and more important, it prevents spread of P. vivaxmalaria.

** Till recently , it was recommended treatment under the NationalMalaria Eradication Programme(now NVBDCP) in India.

What is presumptive treatment?What is presumptive treatment? ****PresumptionPresumption -- In an area with high transmission of malaria, it should In an area with high transmission of malaria, it should be presumed that ALL cases of fever are due to malaria.be presumed that ALL cases of fever are due to malaria.TreatmentTreatment -- First loading dose of First loading dose of chloroquinechloroquine should be administered should be administered immediately after collecting the blood specimen, even without waimmediately after collecting the blood specimen, even without waiting for iting for its report. its report.

If the fever is indeed malaria, this treatment alleviates symptIf the fever is indeed malaria, this treatment alleviates symptoms early, oms early, may be well before the test result is available. may be well before the test result is available.

If it is malaria, If it is malaria, chloroquinechloroquine also prevents the spread of malaria by also prevents the spread of malaria by destroying the gametocytes of P. destroying the gametocytes of P. vivaxvivax (the more common malaria). (the more common malaria).

If it is not malaria, nothing is lost, for If it is not malaria, nothing is lost, for chloroquinechloroquine at this dose is safe at this dose is safe and has no adverse effects.and has no adverse effects.

It cures early and more important, it prevents spread of P. It cures early and more important, it prevents spread of P. vivaxvivaxmalaria.malaria.

**** Till recently , it was recommended treatment under the NationalTill recently , it was recommended treatment under the NationalMalaria Eradication Malaria Eradication Programme(nowProgramme(now NVBDCP) in India.NVBDCP) in India.

THE N

ATION

AL AN

TI MA

LARIA DRUG POLICY‐2010

“APPRO

PRIATE FOR TO

DAY A

ND SAFE FOR

TOMO

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”

THE N

ATION

AL AN

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LARIA DRUG POLICY

THE N

ATION

AL AN

TI MA

LARIA DRUG POLICY‐‐2010

2010

““APPRO

PRIATE FOR TO

DAY A

ND SAFE FOR

APPROPRIATE FOR TO

DAY A

ND SAFE FOR

TOMO

RROW

TOMO

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””


THE NATIONAL ANTI MALARIA DRUG POLICY‐2010 “APPROPRIATE FOR TODAY AND SAFE FOR TOMORROW”

THE NATIONAL ANTI MALARIA DRUG POLICYTHE NATIONAL ANTI MALARIA DRUG POLICY‐‐2010 2010 ““APPROPRIATE FOR TODAY AND SAFE FOR TOMORROWAPPROPRIATE FOR TODAY AND SAFE FOR TOMORROW””

� Providing complete cure (clinical and parasitological) of malaria cases� Prevention of progression of uncomplicated malaria into severe malaria and thereby reduce malaria mortality� Prevention of relapses by administration of radical treatment� Interruption of transmission of malaria by use of gametocytocidal drugs� Preventing development of drug resistance by rational treatment of malaria cases.

�� Providing complete cure (clinical and parasitological) of Providing complete cure (clinical and parasitological) of malaria casesmalaria cases�� Prevention of progression of uncomplicated malaria into Prevention of progression of uncomplicated malaria into severe malaria and thereby reduce malaria mortalitysevere malaria and thereby reduce malaria mortality�� Prevention of relapses by administration of radical Prevention of relapses by administration of radical treatmenttreatment�� Interruption of transmission of malaria by use of Interruption of transmission of malaria by use of gametocytocidalgametocytocidal drugsdrugs�� Preventing development of drug resistance by rational Preventing development of drug resistance by rational treatment of malaria cases.treatment of malaria cases.

Effective treatment of malaria under the National Drug Policy aims at:Effective treatment of malaria under the National Drug Policy aiEffective treatment of malaria under the National Drug Policy aims at:ms at:


All fever cases suspected to be malaria should be investigated by microscopy orRDT.

1. P.vivax cases should be treated with chloroquine for three days and Primaquinefor 14 days. Primaquine is used to prevent relapse but is contraindicated inpregnant women, infants and individuals with G6PD deficiency.Note: Patients should be instructed to report back in case of haematuria or high colored urine /cyanosis or blue coloration of lips and Primaquine should be stopped in such cases. Care should be taken in patients with anaemia.

2. P. falciparum cases should be treated with ACT (Artesunate 3 days +Sulphadoxine-Pyrimethamine 1 day). This is to be accompanied by single doseprimaquine preferably on day 2.

3. Pregnant women with uncomplicated P. falciparum should be treated as follows:� 1st Trimester: Quinine� 2nd & 3rd Trimester: ACT

Note: Primaquine is contra indicated in pregnant woman

All fever cases suspected to be malaria should be investigated bAll fever cases suspected to be malaria should be investigated by microscopy ory microscopy orRDT.RDT.

11.. P.vivaxP.vivax cases should be treated with cases should be treated with chloroquinechloroquine for three days and for three days and PrimaquinePrimaquinefor 14 days. for 14 days. PrimaquinePrimaquine is used to prevent relapse but is contraindicated inis used to prevent relapse but is contraindicated inpregnant women, infants and individuals with G6PD deficiency.pregnant women, infants and individuals with G6PD deficiency.Note: Patients should be instructed to report back in case of Note: Patients should be instructed to report back in case of haematuriahaematuria or high or high colored urine /cyanosis or blue coloration of lips and colored urine /cyanosis or blue coloration of lips and PrimaquinePrimaquine should be should be stopped in such cases. Care should be taken in patients with stopped in such cases. Care should be taken in patients with anaemiaanaemia..

2. 2. P. P. falciparumfalciparum cases should be treated with ACT (cases should be treated with ACT (ArtesunateArtesunate 3 days +3 days +SulphadoxineSulphadoxine--PyrimethaminePyrimethamine 1 day). This is to be accompanied by single dose1 day). This is to be accompanied by single doseprimaquineprimaquine preferably on day 2.preferably on day 2.

3. 3. Pregnant womenPregnant women with uncomplicated P. with uncomplicated P. falciparumfalciparum should be treated as should be treated as follows:follows:�� 1st Trimester: Quinine1st Trimester: Quinine�� 2nd & 3rd Trimester: ACT2nd & 3rd Trimester: ACT

Note:Note: PrimaquinePrimaquine is contra indicated in pregnant womanis contra indicated in pregnant woman

Treatment of uncomplicated malariaTreatment of Treatment of uncomplicateduncomplicated malariamalaria


5. In cases where parasitological diagnosis is not possible due to non-availability of either timely microscopy or RDT, suspected malaria cases will be treated with full course of chloroquine, till the results of microscopy are received. Once theparasitological diagnosis is available, appropriate treatment as per the species, isto be administered.

6. Presumptive treatment with chloroquine is no more recommended.

7. Resistance should be suspected if in spite of full treatment with no history ofvomiting, diarrhoea, patient does not respond within 72 hours, clinically andparasitologically. Such cases not responding to ACT, should be treated with oralquinine with Tetracycline / Doxycycline. These instances should be reported toconcerned District Malaria /State Malaria Officer/ROHFW for initiation oftherapeutic efficacy studies.

5. In cases where parasitological diagnosis is not possible due 5. In cases where parasitological diagnosis is not possible due to nonto non--availability of availability of either timely microscopy or RDT, either timely microscopy or RDT, suspected malaria cases will be treated with full suspected malaria cases will be treated with full course of course of chloroquinechloroquine, till the results of microscopy are received., till the results of microscopy are received. Once theOnce theparasitological diagnosis is available, appropriate treatment asparasitological diagnosis is available, appropriate treatment as per the species, isper the species, isto be administered.to be administered.

6. 6. Presumptive treatment with Presumptive treatment with chloroquinechloroquine is no more recommendedis no more recommended..

7. 7. Resistance should be suspected if in spite of full treatment witResistance should be suspected if in spite of full treatment with no history ofh no history ofvomiting, vomiting, diarrhoeadiarrhoea, patient does not respond within 72 hours, patient does not respond within 72 hours, clinically and, clinically andparasitologicallyparasitologically. Such cases not responding to ACT, should be treated with oral. Such cases not responding to ACT, should be treated with oralquinine with Tetracycline / quinine with Tetracycline / DoxycyclineDoxycycline. These instances should be reported to. These instances should be reported toconcerned District Malaria /State Malaria Officer/ROHFW for initconcerned District Malaria /State Malaria Officer/ROHFW for initiation ofiation oftherapeutic efficacy studies.therapeutic efficacy studies.


1. Chloroquine: 25 mg/kg body weight divided over three days i.e. 10mg/kg on day 1, 10mg/kg on day 2 and 5mg/kg on day 3.

2. Primaquine: 0.25 mg/kg body weight daily for 14 days.

1. 1. ChloroquineChloroquine:: 25 mg/kg body weight divided over 25 mg/kg body weight divided over three days i.e. 10mg/kg on day 1, 10mg/kg on day 2 three days i.e. 10mg/kg on day 1, 10mg/kg on day 2 and 5mg/kg on day 3.and 5mg/kg on day 3.

2. 2. PrimaquinePrimaquine:: 0.25 mg/kg body weight daily for 14 0.25 mg/kg body weight daily for 14 days.days.

DRUG SCHEDULE FOR TREATMENT OF MALARIA UNDER NVBDCP

DRUG SCHEDULE FOR TREATMENT OF MALARIA DRUG SCHEDULE FOR TREATMENT OF MALARIA UNDER NVBDCPUNDER NVBDCP

* * PrimaquinePrimaquine is contraindicated in infants, pregnant women and individuals wis contraindicated in infants, pregnant women and individuals with G6PD deficiency. ith G6PD deficiency. 14 day regimen of 14 day regimen of PrimaquinePrimaquine should be given under supervision.should be given under supervision.


Artemisinin based Combination Therapy (ACT)*� Artesunate 4 mg/kg body weight daily for 3 days

Plus� Sulfadoxine (25 mg/kg body weight) . Pyrimethamine(1.25 mg/kg body weight) on first day.

* ACT is not to be given in 1st trimester of pregnancy.

Artemisinin based Combination Therapy (ACT)*� Artesunate 4 mg/kg body weight daily for 3 days

Plus� Sulfadoxine (25 mg/kg body weight) . Pyrimethamine(1.25 mg/kg body weight) on first day.

* ACT is not to be given in 1st trimester of pregnancy.

Treatment of uncomplicated P.falciparum casesTreatment of uncomplicated Treatment of uncomplicated P.falciparumP.falciparum casescases


Treatment of uncomplicated P.falciparum cases in pregnancy

Treatment of uncomplicated Treatment of uncomplicated P.falciparumP.falciparum cases in cases in pregnancypregnancy

1st Trimester : Quinine salt 10mg/kg 3 times daily for 7 days.Note: Quinine may induce hypoglycemia; pregnant women should not start taking quinine on an empty stomach and should eat regularly, while on quinine treatment.

2nd and 3rd trimester: ACT as per dosage given above.

1st Trimester : Quinine salt 10mg/kg 3 times daily for 7 days.Note: Quinine may induce hypoglycemia; pregnant women should not start taking quinine on an empty stomach and should eat regularly, while on quinine treatment.

2nd and 3rd trimester: ACT as per dosage given above.


Treatment of mixed infections (P.vivax + P.falciparum) cases

Treatment of mixed infections (Treatment of mixed infections (P.vivaxP.vivax + + P.falciparumP.falciparum) ) casescases

All mixed infections should be treated with full course of ACT and

Primaquine 0.25 mg per kg body weight daily for 14 days.

All mixed infections should be treated All mixed infections should be treated with full course of ACT and with full course of ACT and

PrimaquinePrimaquine 0.25 mg per kg body weight 0.25 mg per kg body weight daily for 14 days.daily for 14 days.

35

Treatment of severe malaria cases: Severe malaria is an emergency and treatment should be given as per severity and associated complications which can best be decided by the treating physician. The guidelines for specific antimalarialtherapy is as follows:

Treatment of severe malaria casesTreatment of severe malaria cases: : Severe malariaSevere malaria is an emergency is an emergency and treatment should be given and treatment should be given as per severity and associated complicationsas per severity and associated complications which can which can best be decided by the treating physicianbest be decided by the treating physician. The guidelines for specific . The guidelines for specific antimalarialantimalarialtherapy is as follows:therapy is as follows:

Artesunate: 2.4 mg/kg body weight IV or IM given on admission (time = 0h); then at 12 h and 24 h and then once a day.

(or)� Artemether: 3.2 mg/kg body weight IM given on admission and then 1.6mg/kg body weight per day.(or)� Arteether: 150 mg IM daily for 3 days in adults only (not recommended forchildren).

(or)� Quinine: 20 mg/kg* body weight on admission (IV infusion or divided IMinjection) followed by maintenance dose of 10 mg/kg body weight 8 hourly.The infusion rate should not exceed 5 mg salt/kg body weight per hour.(*loading dose of Quinine i.e. 20mg /kg body weight on admission may not be given if the patient has already received quinine or if the clinician feels inappropriate).

ArtesunateArtesunate:: 2.4 mg/kg body weight IV or IM given on admission (time = 02.4 mg/kg body weight IV or IM given on admission (time = 0h); then at 12 h and 24 h and then once a day.h); then at 12 h and 24 h and then once a day.

(or)(or)�� ArtemetherArtemether: 3.2 mg/kg body weight IM given on admission and then 1.6: 3.2 mg/kg body weight IM given on admission and then 1.6mg/kg body weight per day.mg/kg body weight per day.(or)(or)�� ArteetherArteether:: 150 mg IM daily for 3 days in adults only (not recommended for150 mg IM daily for 3 days in adults only (not recommended forchildren).children).

(or)(or)�� QuinineQuinine: 20 mg/kg* body weight on admission (IV infusion or divided IM: 20 mg/kg* body weight on admission (IV infusion or divided IMinjection) followed by maintenance dose of 10 mg/kg body weight injection) followed by maintenance dose of 10 mg/kg body weight 8 hourly.8 hourly.The infusion rate should not exceed 5 mg salt/kg body weight perThe infusion rate should not exceed 5 mg salt/kg body weight per hour.hour.(*loading dose of Quinine i.e. 20mg /kg body weight on admission(*loading dose of Quinine i.e. 20mg /kg body weight on admission may not be given if the patient has may not be given if the patient has already received quinine or if the clinician feels inappropriatealready received quinine or if the clinician feels inappropriate).).

Note:Note:TheThe parenteralparenteral treatment in severe malaria cases should be treatment in severe malaria cases should be given for given for minimum of 24 hours once started (irrespective of the minimum of 24 hours once started (irrespective of the patient.spatient.s ability to tolerate oral medication earlier than 24 hours).ability to tolerate oral medication earlier than 24 hours).


1.. After parenteral artemisinin therapy, patients will receive a full course of oral ACT for 3 days.

2.. Those patients who received parenteral Quinine therapy should receive:Oral Quinine 10 mg/kg body weight three times a day for 7 days (including the days when parenteralQuinine was administered) plus Doxycycline 3 mg/kg body weight once a day or Clindamycin 10 mg/kg body weight 12-hourly for 7 days

(Doxycycline is contraindicated in pregnant women and children under 8 years of age).

1.. 1.. After After parenteralparenteral artemisininartemisinin therapy, patients will therapy, patients will receive a full course of receive a full course of oral ACToral ACT for 3 days. for 3 days.

2.. 2.. Those patients who received Those patients who received parenteralparenteral Quinine Quinine therapy should receivetherapy should receive::Oral QuinineOral Quinine 10 mg/kg body weight three times a 10 mg/kg body weight three times a day for 7 days (including the days when day for 7 days (including the days when parenteralparenteralQuinine was administered) plus Quinine was administered) plus DoxycyclineDoxycycline 3 3 mg/kg body weight once a day or mg/kg body weight once a day or ClindamycinClindamycin 10 10 mg/kg body weight 12mg/kg body weight 12--hourly for 7 days hourly for 7 days

((DoxycyclineDoxycycline is contraindicated in pregnant women and children under 8 yearsis contraindicated in pregnant women and children under 8 years of age).of age).

Why Why injectableinjectable ArteetherArteether Over Over injectableinjectable ArtesunateArtesunate & & injectableinjectable ArtemetherArtemetherin the National Drug Policy ???in the National Drug Policy ???

1.1. Immediate onset and rapid reduction of Immediate onset and rapid reduction of parasitaemiaparasitaemia with with complete clearance in most cases within 48 hourscomplete clearance in most cases within 48 hours

2.2. Clinical recovery of the patient, e.g. Clinical recovery of the patient, e.g. defervescencedefervescence is faster is faster than with other than with other antimalarialsantimalarials..

3.3. Therapeutically equivalent to quinine in cerebral malariaTherapeutically equivalent to quinine in cerebral malaria4.4. More More lipophiliclipophilic properties than properties than artemetherartemether favouringfavouring

accumulation in brain tissue and thus the treatment of accumulation in brain tissue and thus the treatment of cerebral malaria were regarded as advantages over the other cerebral malaria were regarded as advantages over the other compounds.compounds.

5.5. ArteetherArteether has much slower has much slower elimination.[eliminationelimination.[elimination halfhalf6.6. life:life:ArteetherArteether--20 hrs20 hrs;;ArtemetherArtemether--6hrs6hrs;;ArtesunateArtesunate--1hr1hr]]

Inj.ARTEETHERInj.ARTEETHER::

Comparative Efficacy :In Cerebral Malaria

Parameter Arteether Quinine

Coma recovery time (hrs.)

Mortality (%)

24.33

6.67

38.87

27.27

Important for RxImportant for RxImportant for Rx

Most blood schizonticidal drugs prevent the development of the forthcoming erythrocytic cycle of parasitic development and hence have no or little effect on the ongoing cycle that is already causing fever. Therefore, it would take at least 48 hours for the treatment to be effective.

In severe P. falciparum malaria, oral antimalarials should not be used. Vomiting, poor general health, poor compliance, erratic G.I. absorption due to splanchnic vasculopathy etc. make oral therapy less reliable. Therefore, use only parenteral antimalarials. This also means that oral only antimalarials like Mefloquine and Halofantrinehave no place in treating severe falciparum malaria.

In all cases of P. falciparum malaria, the antimalarial drugs should be chosen depending on the severity of the illness and the sensitivity pattern in the locality. Changing the drugs or adding the drugs in between is not advisable.

Most blood Most blood schizonticidalschizonticidal drugs prevent the development of the drugs prevent the development of the forthcoming forthcoming erythrocyticerythrocytic cycle of parasitic development and hence cycle of parasitic development and hence have no or little effect on the ongoing cycle that is already cahave no or little effect on the ongoing cycle that is already causing using fever. Therefore, fever. Therefore, it would take at least 48 hours for the treatment to it would take at least 48 hours for the treatment to be effective.be effective.

In severe In severe P. P. falciparumfalciparum malaria, oral malaria, oral antimalarialsantimalarials should not be should not be used. Vomiting, poor general health, poor compliance, erratic G.used. Vomiting, poor general health, poor compliance, erratic G.I. I. absorption due to absorption due to splanchnicsplanchnic vasculopathyvasculopathy etc. make oral therapy etc. make oral therapy less reliable. Therefore, use only less reliable. Therefore, use only parenteralparenteral antimalarialsantimalarials. This also . This also means that means that oral only oral only antimalarialsantimalarials like like MefloquineMefloquine and and HalofantrineHalofantrinehave no place in treating severe have no place in treating severe falciparumfalciparum malaria. malaria.

In all cases of In all cases of P. P. falciparumfalciparum malaria, the malaria, the antimalarialantimalarial drugs should drugs should be chosen depending on the be chosen depending on the severity of the illness and the severity of the illness and the sensitivity pattern in the localitysensitivity pattern in the locality. . Changing the drugs or adding the Changing the drugs or adding the drugs in between is not advisable. drugs in between is not advisable.


Most antimalarial drugs have a long plasma half-life. Therefore, adding similar drugs half way through the treatment will only add to the adverse effects and not to the therapeutic benefit. The following combinations should therefore be avoided, concurrently or within a short interval:

Do not exceed the maximum recommended dose of antimalarialdrugs. All antimalarial drugs have a narrow safety range and excess dose may lead to adverse effects. Moreover, larger dose does not offer any superior antimalarial effect.

Most Most antimalarialantimalarial drugs have a long drugs have a long plasma halfplasma half--life. Therefore, life. Therefore, adding adding similar drugs half way through the similar drugs half way through the treatmenttreatment will only add to the will only add to the adverse effectsadverse effects and not to the and not to the therapeutic benefit. The following therapeutic benefit. The following combinations combinations should therefore be should therefore be avoidedavoided, concurrently or within a short , concurrently or within a short interval:interval:

Do not exceed the maximum Do not exceed the maximum recommended dose of recommended dose of antimalarialantimalarialdrugs. drugs. All All antimalarialantimalarial drugs have a drugs have a narrow safety range and excess narrow safety range and excess dose may lead to adverse effectsdose may lead to adverse effects. . Moreover, Moreover, larger dose does not offer larger dose does not offer any superior any superior antimalarialantimalarial effect. effect.

…..Important for Rx……..Important for Rx..Important for RxChloroquine + Quinine

Chloroquine + Mefloquine

Quinine + Mefloquine

Quinine + Primaquine

Quinine + Halofantrine

Mefloquine + Primaquine

Administration of Primaquine and Pyrimethamine/sulphadoxine on the same day is also not advisable. Both sulpha and primaquine can precipitate hemolytic crisis in patients with Glucose 6-phosphate dehydrogenase deficiency.

ChloroquineChloroquine + Quinine+ Quinine

ChloroquineChloroquine + + MefloquineMefloquine

Quinine + Quinine + MefloquineMefloquine

Quinine + Quinine + PrimaquinePrimaquine

Quinine + Quinine + HalofantrineHalofantrine

MefloquineMefloquine + + PrimaquinePrimaquine

Administration of Administration of PrimaquinePrimaquine and and Pyrimethamine/sulphadoxinePyrimethamine/sulphadoxine on the on the same day is also not advisablesame day is also not advisable. Both . Both sulphasulpha and and primaquineprimaquine can can precipitate hemolytic crisis in precipitate hemolytic crisis in patients with patients with Glucose 6Glucose 6--phosphate phosphate dehydrogenasedehydrogenase deficiency.deficiency.


http://www.malariasite.com/malaria/G6PD.htm




Primaquine should be administered to ALL cases of malaria as radical treatment except in the following situations where it is contraindicated:

Do not misuse the newer antimalarialdrugs. We need to preserve them for future.

PrimaquinePrimaquine should should be administered to ALL be administered to ALL cases of malaria as cases of malaria as radical treatment except radical treatment except in the following in the following situations where it is situations where it is contraindicated:contraindicated:

Do not misuse the Do not misuse the newer newer antimalarialantimalarialdrugs.drugs. We need to We need to preserve them for future. preserve them for future.

……..Important for Rx…………..Important for Rx..Important for Rx

Pregnancy and lactation

Infants below one year of age. In these two categories, chloroquine should be given every week as a suppressive chemoprophylaxis to prevent relapse of vivax malaria. When these patients are fit for administration of primaquine, they should be given full therapeutic dose of chloroquine as well as primaquine.

Patients with known Glucose 6-phosphate dehydrogenase deficiency

Concurrently with quinine, mefloquine and halofantrine

It should not be used on the same day with sulphadoxine. In such cases it can be given the next day.

Pregnancy and lactation Pregnancy and lactation

Infants below one year of age. In these two Infants below one year of age. In these two categories, categories, chloroquinechloroquine should be given every week should be given every week as a suppressive chemoprophylaxis to prevent as a suppressive chemoprophylaxis to prevent relapse of relapse of vivaxvivax malaria. When these patients are fit malaria. When these patients are fit for administration of for administration of primaquineprimaquine, they should be , they should be given full therapeutic dose of given full therapeutic dose of chloroquinechloroquine as well as as well as primaquineprimaquine..

Patients with known Glucose 6Patients with known Glucose 6--phosphate phosphate dehydrogenasedehydrogenase deficiencydeficiency

Concurrently with quinine, Concurrently with quinine, mefloquinemefloquine and and halofantrinehalofantrine

It should not be used on the same day with It should not be used on the same day with sulphadoxinesulphadoxine. In such cases it can be given the next . In such cases it can be given the next day. day.

Research into newer antimalarial drugs is scanty and the parasite is fast developing resistance even for newer drugs. Thus if we deplete the newer drugs by misusing them, we may not have anything left for treating ALL DRUG RESISTANT malaria in the not-too-far-future.

Therefore, newer anti malarial drugs should be used only when definitely indicated and not indiscriminately.

These drugs should be used ONLY when parasite index or other methods PROVE drug resistant malaria.

In addition, artemisinin derivatives can be used in cases of hyperparasitemia or life-threatening complications on account of their ability to clear the parasitemia earlier compared to other anti malarial drugs.

Research into newer Research into newer antimalarialantimalarial drugs is scanty drugs is scanty and the parasite is fast developing resistance even and the parasite is fast developing resistance even for newer drugs. Thus if we deplete the newer drugs for newer drugs. Thus if we deplete the newer drugs by misusing them, we may not have anything left for by misusing them, we may not have anything left for treating ALL DRUG RESISTANT malaria in the nottreating ALL DRUG RESISTANT malaria in the not--tootoo--farfar--future. future.

Therefore, newer anti malarial drugs should be Therefore, newer anti malarial drugs should be used only when definitely indicated and not used only when definitely indicated and not indiscriminately. indiscriminately.

These drugs should be used ONLY when These drugs should be used ONLY when parasite index or other methods PROVE drug parasite index or other methods PROVE drug resistant malaria.resistant malaria.

In addition, In addition, artemisininartemisinin derivatives can be used derivatives can be used in cases of in cases of hyperparasitemiahyperparasitemia or lifeor life--threatening threatening complications on account of their ability to clear the complications on account of their ability to clear the parasitemiaparasitemia earlier compared to other anti malarial earlier compared to other anti malarial drugs. drugs. Dr.G.C Sahu/ROHFW/GoI/A'Bad

While most of the the clinical manifestations of malaria are caused by the malarial infection per se………………

• High grade fever as well as the side effects of anti malarial therapy can also contribute to the clinical manifestations.

• All these may act in unison, further confusing the picture.

• In some cases, secondary infections like pneumonia or urinary tract infection can add to the woes.

All the above facts should always be kept in mind.

While most of the While most of the thethe clinical manifestations clinical manifestations of malaria are caused by the malarial of malaria are caused by the malarial infection per seinfection per se………………………………

•• High grade fever as well as the side effects High grade fever as well as the side effects of anti malarial therapy can also contribute of anti malarial therapy can also contribute to the clinical manifestations. to the clinical manifestations.

•• All these may act in unison, further All these may act in unison, further confusing the picture.confusing the picture.

•• In some cases, secondary infections like In some cases, secondary infections like pneumonia or urinary tract infection can add pneumonia or urinary tract infection can add to the woes. to the woes.

All the above facts should All the above facts should always be kept in mind.always be kept in mind.


Artemisinin based combinations are known to improve cure rates, reduce the development of resistance and they might decrease transmission of drug-resistant

parasites. The total effect of artemisinin combinations (which can be simultaneous or sequential) is to reduce the chance of parasite recrudescence, reduce the within-

patient selection pressure, and prevent transmission.

ArtemisininArtemisinin based combinations are known to improve cure rates, reduce the based combinations are known to improve cure rates, reduce the development of resistance and they might decrease transmission odevelopment of resistance and they might decrease transmission of drugf drug--resistant resistant

parasites. The total effect of parasites. The total effect of artemisininartemisinin combinations (which can be simultaneous or combinations (which can be simultaneous or sequential) sequential) is is to reduce the chance of parasite recrudescence, reduce the withito reduce the chance of parasite recrudescence, reduce the withinn--

patient selection pressure, and prevent transmissionpatient selection pressure, and prevent transmission..

Artemisinin based combinations- 1 ArtemisininArtemisinin based combinationsbased combinations-- 1 1

Efficacy Efficacy Very high Very high chloroquinechloroquine failure failure rates (>60%) and subrates (>60%) and sub--optimal optimal efficacy of the combination efficacy of the combination

(<85% cure rate)(<85% cure rate)

Status Status Not approved; Not a viable Not approved; Not a viable option in areas with preoption in areas with pre--

existing moderate to high existing moderate to high levels of P. levels of P. falciparumfalciparum

resistance to resistance to ChloroquineChloroquine

Artesunate + ChloroquineArtesunateArtesunate + + ChloroquineChloroquine


Artemisinin based combinations - 2ArtemisininArtemisinin based combinations based combinations -- 22

Efficacy and advantagesEfficacy and advantages Well tolerated; Efficacy Well tolerated; Efficacy dependent on the level of predependent on the level of pre--

existing resistance to SPexisting resistance to SPDisadvantagesDisadvantages Pharmacokinetic mismatch; Pharmacokinetic mismatch;

adverse effects to SPadverse effects to SP

Dose Dose ArtesunateArtesunate 4mg/kg once daily 4mg/kg once daily for 3 days and SP single dose for 3 days and SP single dose

of 25mg/kg and 1.25mg/kg of 25mg/kg and 1.25mg/kg respectivelyrespectively

Status Status Approved (in areas where SP Approved (in areas where SP efficacy is high); Resistance to efficacy is high); Resistance to

SP limits the useSP limits the use

Artesunate + Sulfadoxine/Pyrimethamine (SP)ArtesunateArtesunate + + Sulfadoxine/PyrimethamineSulfadoxine/Pyrimethamine (SP)(SP)


Artemisinin based combinations - 3ArtemisininArtemisinin based combinations based combinations -- 33

Efficacy and advantages Efficacy and advantages As effective, and better As effective, and better tolerated, as tolerated, as artesunateartesunate plus plus

mefloquinemefloquine; No serious ; No serious

adverse reactions documentedadverse reactions documented

Disadvantages Disadvantages ?Irreversible hearing ?Irreversible hearing impairment impairment

Dose Dose ArtemetherArtemether 1.5mg/kg and 1.5mg/kg and LumifantrineLumifantrine 9mg/kg at 0, 8, 24, 9mg/kg at 0, 8, 24,

36, 48 and 60 hours36, 48 and 60 hours

Status Status Approved; Not recommended Approved; Not recommended for use in pregnancy and for use in pregnancy and

lactating women lactating women

Artemether + Lumefantrine (Coartem,TM RiametTM) ArtemetherArtemether + + LumefantrineLumefantrine ((Coartem,TMCoartem,TM RiametTMRiametTM) )


Combination therapies recommended by WHO

•• ArtesunateArtesunate + + amodiaquineamodiaquine

•• Artemether/LumefantrineArtemether/Lumefantrine

•• ArtesunateArtesunate + SP+ SP

•• ArtesunateArtesunate + + mefloquinemefloquine

FDCFDC

ACTsACTs


How and when can How and when can ArtemisininArtemisinin drugs drugs be affordable for most malaria patients be affordable for most malaria patients

in the world?in the world?

Using compounds to replace the single-ingredient drugs should be recommended.

ArtemisininArtemisinin drugs Alonedrugs Alone：：•• High consuming of High consuming of ArtemisininArtemisinin•• High costHigh cost•• Long treatment course Long treatment course ArtemisininArtemisinin compounds(ACTcompounds(ACT))：：•• Low consuming of Low consuming of artemisininartemisinin•• Lower cost Lower cost •• Short treatment courseShort treatment course•• Low recrudescence, easy to finish the complete Low recrudescence, easy to finish the complete

treatment course.treatment course.

Parasitological rationale for combination treatment

• If for example 1 of 106 parasites is resistant to treatment A and 1 of 106

parasites is resistant to treatment B, then 1 of 1012 will be resistant to both.

• A typical malaria patient would have 1010

parasites

Practical rationale for Practical rationale for combination therapycombination therapy

•• Most of the Most of the artemisininartemisinin drug combination drug combination regimens last 3 days and are well toleratedregimens last 3 days and are well tolerated

•• Hence high complianceHence high compliance•• High compliance + high efficacy = high High compliance + high efficacy = high

effectivenesseffectiveness•• High effectiveness means long durabilityHigh effectiveness means long durability•• Long durability means rarer policy changes Long durability means rarer policy changes

with their inevitable costs and woeswith their inevitable costs and woes


51

Quick comparison between blood schizonticidal drugsQuick comparison between blood Quick comparison between blood schizonticidalschizonticidal drugsdrugsChloroquineChloroquine Sulpha/PyriSulpha/Pyri QuinineQuinine MefloquineMefloquine QuinghasuQuinghasu

EfficacyEfficacy ++++++++ ++++ ++++++ ++++++ +++++++++++++++

Onset of actionOnset of action RapidRapid SlowSlow RapidRapid RapidRapid FastestFastestFastest

UseUse

Prototype drug, Prototype drug, first choice for all first choice for all

casescases

Only for Only for uncomplicated, uncomplicated, resistantresistantP. P. falciparumfalciparum

Only for resistantOnly for resistantP. P. falciparumfalciparum

Only for Only for uncomplicated, multi uncomplicated, multi drug resistantdrug resistantP. P. falciparumfalciparum

Reserved for drug Reserved for drug resistantresistant

P. P. falciparumfalciparum. However, it . However, it may be considered in life may be considered in life

threatening complications threatening complications of P. of P. falciparumfalciparum due to its due to its

rapid actionrapid action

Use in severeUse in severeP. P. falciparumfalciparum

malariamalaria

ParenteralParenteralpreparation can be preparation can be used in areas with used in areas with sensitive strainssensitive strains

Not useful in acute Not useful in acute illness; can be coillness; can be co--prescribed with prescribed with other other parenteralparenteralantimalarialsantimalarials

Drug of choice for Drug of choice for severe malaria; it was severe malaria; it was the only the only parenteralparenteraldrug available for a drug available for a long time until long time until parenteralparenteral chloroquinechloroquineand and artemisininartemisininarrivedarrived

Not to be used in Not to be used in acute illness; can be acute illness; can be coco--prescribed with prescribed with artemisininartemisinin after after acute phase is over.acute phase is over.

Useful in severe Useful in severe malaria; may be malaria; may be more effective and more effective and better tolerated than better tolerated than quinine.quinine.

ToxicityToxicity ++++ ++++++ ++++++ ++++++ ++

Contra indicationsContra indicationsAlmost none, only Almost none, only

advanced liver advanced liver diseasedisease

Allergy to Allergy to sulphasulpha Prior hypersensitive Prior hypersensitive reactionsreactions

Epilepsy, psychosis, Epilepsy, psychosis, heart block, heart block, ßß blocker blocker useuse

NoneNone

Use in pregnancyUse in pregnancy YesYes Only in 2Only in 2ndnd trimester trimester if warrantedif warranted

Only if warranted, Only if warranted, watch for watch for hypoglycemiahypoglycemia

Not in first trimesterNot in first trimester Yes, if the situation demands

Yes, if the situation Yes, if the situation demandsdemands

CostCost CheapestCheapest CheapCheap ModerateModerate ExpensiveExpensive ExpensiveExpensive

Malaria Parasite ResistanceMalaria Parasite Resistance• Mechanism of resistance is due to genetic

mutations in malaria parasite

ResistanceResistanceResistance

Delayed ResponseDelayed Response

Recurrence of InfectionRecurrence of Infection

Increased GametocyteIncreased GametocyteIncrease TransmissionIncrease Transmission

Increased Clinical CasesIncreased Clinical Cases

More Drug UsedMore Drug Used



The Acts of Commissions And Omissions IN MALARIA.The Acts of Commissions And Omissions IN MALARIA.The Acts of Commissions And Omissions IN MALARIA.

Mis-diagnosis MisMis--diagnosis diagnosis

Over-diagnosisObsession with malaria

and forgetting the OTHER causes of fever

OverOver--diagnosisdiagnosisObsession with malaria Obsession with malaria

and forgetting the OTHER and forgetting the OTHER causes of fevercauses of fever

In an endemic area, there may be a tendency to diagnose all cases of fever as malaria, forgetting to even consider other causes. Whereas presumptive treatment with chloroquine in cases of fever is well accepted, sometimes, doctors may go beyond that and indulge in presumptive treatment with newer drugs, (reserved for multi drugresistance falciparum malaria), even if the MP test is repeatedly negative. Most often such cases turn out to be non-malarial fevers. Therefore consider other causes of fever.

In an endemic area, there may be a tendency to diagnose all caseIn an endemic area, there may be a tendency to diagnose all cases of s of fever as malaria, forgetting to even consider other causes. Wherfever as malaria, forgetting to even consider other causes. Whereas eas presumptive treatment with presumptive treatment with chloroquinechloroquine in cases of fever is well in cases of fever is well accepted, sometimes, doctors may go beyond that and indulge in accepted, sometimes, doctors may go beyond that and indulge in presumptive treatment with newer drugs, (reserved for multi drugpresumptive treatment with newer drugs, (reserved for multi drugresistance resistance falciparumfalciparum malaria), even if the MP test is repeatedly malaria), even if the MP test is repeatedly negative. Most often such cases turn out to be nonnegative. Most often such cases turn out to be non--malarial fevers. malarial fevers. Therefore consider other causes of fever.Therefore consider other causes of fever.

Under-diagnosisForgetting malariaUnderUnder--diagnosisdiagnosis

Forgetting malariaForgetting malaria

1. Malaria may not be considered as a possibility in places where it is not common-history of travel to malarious area should be elicited.

2. It may not be considered in patients on chemoprophylaxis for malaria. Chemoprophylaxis does not offer 100% protection and malaria should be therefore looked for in these patients.

3. Malaria can always co-exist with other infections in an endemic area. Therefore, it should be considered even in patients with other obvious infections causing fever.

1. 1. Malaria may not be considered as a possibility in places where iMalaria may not be considered as a possibility in places where it is t is not commonnot common--history of travel to history of travel to malariousmalarious area should be elicited.area should be elicited.

22. It may not be considered in patients on chemoprophylaxis for . It may not be considered in patients on chemoprophylaxis for malaria. Chemoprophylaxis does not offer 100% protection and malmalaria. Chemoprophylaxis does not offer 100% protection and malaria aria should be therefore looked for in these patients.should be therefore looked for in these patients.

3.3. Malaria can always coMalaria can always co--exist with other infections in an endemic area. exist with other infections in an endemic area. Therefore, it should be considered even in patients with other oTherefore, it should be considered even in patients with other obvious bvious infections causing fever.infections causing fever.


Mis-reportMisMis--reportreport

False positiveFalse positiveFalse positive

Artifacts may be read as malarial parasites on peripheral smear as well as QBC test. Dirty slides, contaminated stains, inexperienced microscopist, recycled QBC tubes may be the causes.

Artifacts may be read as malarial parasites on Artifacts may be read as malarial parasites on peripheral smear as well as QBC test. Dirty peripheral smear as well as QBC test. Dirty slides, contaminated stains, inexperienced slides, contaminated stains, inexperienced microscopistmicroscopist, recycled QBC tubes may be the , recycled QBC tubes may be the causes.causes.

False negativeFalse negativeFalse negative

Malarial parasites may be missed and the test reported as negative. Inadequate smear, dirty stains, contaminated/deteriorated stains, wrong buffer pH, inexperienced technician, incomplete examination of the slide, storage of blood in anticoagulant before preparing the smear etc. may contribute to this problem.

Malarial parasites may be missed and the test Malarial parasites may be missed and the test reported as negative. Inadequate smear, dirty reported as negative. Inadequate smear, dirty stains, contaminated/deteriorated stains, stains, contaminated/deteriorated stains, wrong buffer pH, inexperienced technician, wrong buffer pH, inexperienced technician, incomplete examination of the slide, storage of incomplete examination of the slide, storage of blood in anticoagulant before preparing the blood in anticoagulant before preparing the smear etc. may contribute to this problem.smear etc. may contribute to this problem.


Mis-judgement of severityMisMis--judgementjudgement of severityof severity

Over-estimationOverOver--estimationestimation

Panic reaction to P. falciparum malaria is common among patients and not uncommon among doctors, resulting in over-reaction to the situation and over-treatment. Mild anemia, mild icterus, headache etc. are common in falciparum malaria and need not necessarily imply severe malaria. Such patients need not be treated with parenteral or second line antimalarial drugs. Also it should not be forgotten that some of the manifestations could be due to fever, drugs etc., and not necessarily due to severe malaria.

Panic reaction to Panic reaction to P. P. falciparumfalciparum malaria is common among malaria is common among patients and not uncommon among doctors, resulting in patients and not uncommon among doctors, resulting in overover--reaction to the situation and overreaction to the situation and over--treatment. Mild treatment. Mild anemia, mild anemia, mild icterusicterus, headache etc. are common in , headache etc. are common in falciparumfalciparum malaria and need not necessarily imply severe malaria and need not necessarily imply severe malaria. Such patients need not be treated with malaria. Such patients need not be treated with parenteralparenteral or or second line second line antimalarialantimalarial drugs. Also it should not be drugs. Also it should not be forgotten that some of the manifestations could be due to forgotten that some of the manifestations could be due to fever, drugs etc., and not necessarily due to severe malaria.fever, drugs etc., and not necessarily due to severe malaria.

Under-estimationUnderUnder--estimationestimation

P. falciparum malaria can cause dramatic complications and therefore one should be always looking for them. Patients who are at for development of complications should be ideally admitted for observation. Any indication of complication should be properly managed. Neglecting the signs like high fever, prostration, significant pallor and jaundice, dehydration etc. may prove costly. Hypoglycemia may be easily missed.

P. P. falciparumfalciparum malaria can cause dramatic complications and malaria can cause dramatic complications and therefore one should be always looking for them. Patients therefore one should be always looking for them. Patients who are at for development of complications should be who are at for development of complications should be ideally admitted for observation. Any indication of ideally admitted for observation. Any indication of complication should be properly managed. Neglecting the complication should be properly managed. Neglecting the signs like high fever, prostration, significant pallor and signs like high fever, prostration, significant pallor and jaundice, dehydration etc. may prove costly. Hypoglycemia jaundice, dehydration etc. may prove costly. Hypoglycemia may be easily missed.may be easily missed.


IT MUST ALWAYS BE REMEMBERED THAT MALARIA IS A LOCAL PHENOMENA AND ITS FOCAL NATURE IS DETERMINED BY

THE FLIGHT RANGE OF THE LOCAL VECTOR(S)POPULATION .

AS LONG AS MALARIA PARASITES REMAIN IN THE HUMAN BODY, IT IS MORE OR LESS PROTECTED FROM THE ENVIRONMENT AND ITS DEVELOPMENT CONTINUES UNABATED EXCEPT FOR THE

INFLUENCE OF THE IMMUNITY OR ADMINISTRATION OF APPRPRIATE ANTI-MALARIA DRUGS .

IT MUST ALWAYS BE REMEMBERED THAT MALARIA IS A IT MUST ALWAYS BE REMEMBERED THAT MALARIA IS A LOCAL PHENOMENALOCAL PHENOMENA AND ITS AND ITS FOCAL NATUREFOCAL NATURE IS DETERMINED BY IS DETERMINED BY

THE THE FLIGHT RANGEFLIGHT RANGE OF THE LOCAL VECTOR(S)POPULATION .OF THE LOCAL VECTOR(S)POPULATION .

AS LONG AS MALARIA PARASITES REMAIN IN THE HUMAN AS LONG AS MALARIA PARASITES REMAIN IN THE HUMAN BODY, IT IS MORE OR LESS PROTECTED FROM THE ENVIRONMENT BODY, IT IS MORE OR LESS PROTECTED FROM THE ENVIRONMENT AND ITS DEVELOPMENT CONTINUES UNABATED AND ITS DEVELOPMENT CONTINUES UNABATED EXCEPT FOR THE EXCEPT FOR THE

INFLUENCEINFLUENCE OF THE IMMUNITY OR ADMINISTRATION OF OF THE IMMUNITY OR ADMINISTRATION OF APPRPRIATE ANTIAPPRPRIATE ANTI--MALARIA DRUGSMALARIA DRUGS ..


……..And..And

ADDITIONALADDITIONAL INFORMATIONSINFORMATIONS

ParasitemiaParasitemia Parasites Parasites ccmccm/ l/ l RemarksRemarks

0.00010.0001--0.0004%0.0004% 55--2020 Sensitivity of thick blood filmSensitivity of thick blood film

0.002%0.002% 100100 Patients may have symptoms below this level, where malaria is sePatients may have symptoms below this level, where malaria is seasonalasonal

0.2%0.2% 10,00010,000 Level above which immunes show symptomsLevel above which immunes show symptoms

2%2% 100,000100,000 Maximum Maximum parasitemiaparasitemia of of P.vivaxP.vivax. and . and P.ovaleP.ovale

22--5%5% 100,000100,000--250,000250,000 HyperparasitemiaHyperparasitemia/severe malaria*, increased mortality/severe malaria*, increased mortality

10%10% 500,000500,000 Exchange transfusion may be considered/high mortalityExchange transfusion may be considered/high mortality

* * WHO criteria for severe malaria are WHO criteria for severe malaria are parasitemiaparasitemia > 10,000 / l and severe anemia (> 10,000 / l and severe anemia (HbHb < 5 < 5 g/lg/l). Prognosis ). Prognosis is poor if > 20% parasites are pigment containing is poor if > 20% parasites are pigment containing trophozoitestrophozoites and and schizontsschizonts and/or if > 5% of and/or if > 5% of

neutrophilsneutrophils contain visible pigment. contain visible pigment.

Level of parasitemia and clinical correlatesLevel of Level of parasitemiaparasitemia and clinical correlatesand clinical correlates



Examination of blood smear

Demonstration of the parasite in a smear of the blood definitely establishes the presence of malaria.

A negative finding on examination does not rule out malaria. Only 50% of children with malaria are smear positive, even on repeated examination.

A positive finding on examination does not confirm clinical malaria,especially in patients from an endemic area, in whom a symptomatic parasitemiaoften exists.

Both thick and thin films are essential. If the parasitemia is light, a thin film examination may miss the diagnosis. Thick films save time in diagnosis of scanty infections but make species identification of the parasite difficult.

At least 100-200 fields of a thick film should be scrutinized before a slide is reported as negative for malaria. In doubtful cases, the examination can be repeated after 4 hours.

Various techniques to enhance the diagnostic utility of the peripheral blood smear examination are in use. Fluorescent staining and microscopy, centrifugation, selective magnetic separation techniques, and other techniques have been used but have only a moderate effect.

Examination of blood smearExamination of blood smear

Demonstration of the parasite in a smear of the blood Demonstration of the parasite in a smear of the blood definitely establishes definitely establishes the presence of malaria.the presence of malaria.

A negative finding on examination does not rule out malariaA negative finding on examination does not rule out malaria. Only 50% . Only 50% of children with malaria are smear positive, even on repeated exof children with malaria are smear positive, even on repeated examination.amination.

A positive finding on examination does not confirm clinical malaA positive finding on examination does not confirm clinical malariaria,,especially in patients from an endemic area, in whom a symptomatespecially in patients from an endemic area, in whom a symptomatic ic parasitemiaparasitemiaoften exists.often exists.

Both thick and thin films are essentialBoth thick and thin films are essential. If the . If the parasitemiaparasitemia is light, a thin film is light, a thin film examination may miss the diagnosis. Thick films save time in diaexamination may miss the diagnosis. Thick films save time in diagnosis of scanty gnosis of scanty infections but make species identification of the parasite diffiinfections but make species identification of the parasite difficult.cult.

At least 100At least 100--200 fields of a thick film should be scrutinized before a 200 fields of a thick film should be scrutinized before a slide is reported as negative for malariaslide is reported as negative for malaria.. In doubtful cases, the examination In doubtful cases, the examination can be repeated after 4 hours.can be repeated after 4 hours.

Various techniques to enhance the diagnostic utility of the perVarious techniques to enhance the diagnostic utility of the peripheral blood smear ipheral blood smear examination are in use. Fluorescent staining and microscopy, cenexamination are in use. Fluorescent staining and microscopy, centrifugation, trifugation, selective magnetic separation techniques, and other techniques hselective magnetic separation techniques, and other techniques have been used but ave been used but have only a moderate effect.have only a moderate effect.


Treatment of P. vivax malaria: A flow chart

61

Treatment of Treatment of P. P. vivaxvivax malaria: A flow chartmalaria: A flow chartChloroquineChloroquine + + PrimaquinePrimaquine

After 48 hoursAfter 48 hours

Clinical RecoveryClinical Recovery Status quo / worseStatus quo / worseContinue the treatmentContinue the treatmentRepeat the M.P. test on Repeat the M.P. test on

the 6the 6thth dayday

Suspect P. Suspect P. falciparumfalciparum, repeat M.P. test, repeat M.P. test at 48 at 48 hrs.hrs.

(A thin smear examination is better for species (A thin smear examination is better for species identification and for assessing parasite count)identification and for assessing parasite count)

NEGATIVENEGATIVE POSITIVEPOSITIVECuredCured POSITIVEPOSITIVE NEGATIVENEGATIVE

Consider Consider other causes other causes of fever, may of fever, may be in be in association association with malaria with malaria

P. P. FalciparumFalciparumTreat as possibly Treat as possibly

chloroquinechloroquine resistantresistant

P. P. VivaxVivaxIf the patient has If the patient has typical malarial typical malarial

complications, treat as complications, treat as P. P. falciparumfalciparum; ;

otherwise, wait.otherwise, wait.


Treatment of P. falciparum malaria -A flow chartTreatment of Treatment of P. P. falciparumfalciparum malaria malaria --A flow chartA flow chart

Uncomplicated and chloroquinesensitive

Uncomplicated and Uncomplicated and chloroquinechloroquinesensitivesensitive

Complicated and chloroquine sensitive

Complicated and Complicated and chloroquinechloroquine sensitivesensitive

Tab. Chloroquine + Primaquinesingle dose

Tab. Tab. ChloroquineChloroquine + + PrimaquinePrimaquinesingle dosesingle dose

Inj. Chloroquine + Primaquine single dose

InjInj. . ChloroquineChloroquine + + PrimaquinePrimaquine single dosesingle dose

Better; parasite count reduced by > 75%

Better; parasite count reduced by Better; parasite count reduced by > 75%> 75%

Status quo/ worse; parasite count reduced

by < 75%

Status quo/ worse; Status quo/ worse; parasite count reduced parasite count reduced

by < 75%by < 75%

ContinueContinueContinue Consider resistanceConsider resistanceConsider resistance

Dr.G.C Sahu/ROHFW/GoI/A'Bad63

Drugs for chloroquine resistant Pf malariaDrugs for Drugs for chloroquinechloroquine resistant resistant Pf Pf malariamalaria

Uncomplicated and Chloroquine resistantUncomplicated and Uncomplicated and

ChloroquineChloroquine resistantresistant

Complicated and

Chloroquineresistant

Complicated Complicated and and

ChloroquineChloroquineresistantresistant

Use any one of the following combinations: 1. Tab.Quinine + Tab. Pyrimethamine/ Sulfa.2. Tab. Quinine + Tetracycline /doxycycline

3. Tab. Artesunate + Tab. Mefloquine4.Tab.Mefloquine + Pyrimethamine/Sulpha.

Use any one of the following combinations: Use any one of the following combinations: 1. 1. Tab.QuinineTab.Quinine + Tab. + Tab. PyrimethaminePyrimethamine/ Sulfa./ Sulfa.2. Tab. Quinine + Tetracycline /2. Tab. Quinine + Tetracycline /doxycyclinedoxycycline

3. Tab. 3. Tab. ArtesunateArtesunate + Tab. + Tab. MefloquineMefloquine4.Tab.Mefloquine + 4.Tab.Mefloquine + Pyrimethamine/SulphaPyrimethamine/Sulpha..

1. Inj.Quinine + Pyrimethamine/Sulphadoxine2. Inj. Quinine + Tetracycline /

Doxycycline3. Inj. Artemether / Arteether /

Artesunate + Mefloquine.

1. 1. Inj.QuinineInj.Quinine + + Pyrimethamine/SulphadoxinePyrimethamine/Sulphadoxine2. 2. InjInj. Quinine + Tetracycline / . Quinine + Tetracycline /

DoxycyclineDoxycycline3. 3. InjInj. . ArtemetherArtemether / / ArteetherArteether / /

ArtesunateArtesunate + + MefloquineMefloquine..


Clinical approach to cases of recurrent malariaClinical approach to cases of recurrent malaria

RecurrenceRecurrence Within 8Within 8--10 10 daysdays

After 2 After 2 weeksweeks

After 2 After 2 monthsmonths

11stst

possibilitypossibility?P. ?P. falciparumfalciparum ?Re?Re--infectioninfection ?Re?Re--infectioninfection

22ndnd

possibilitypossibility?Compliance?Compliance ?P. ?P. falciparumfalciparum ?Relapse?Relapse


Established Established antimalarialantimalarial drugsdrugsDrugDrugDrug RoleRoleRole Best features(s)Best Best features(sfeatures(s)) LimitationLimitationLimitation

ChloroquineChloroquineChloroquine TX of and CP against non-Pf and sensitive Pf parasitesTX of and CP against nonTX of and CP against non--Pf Pf and sensitive Pf parasitesand sensitive Pf parasites

Very safe; low cost; long half-lifeVery safe; low cost; Very safe; low cost; long halflong half--lifelife

Widespread RWidespread RWidespread R

Quinine/quinidineQuinine/Quinine/quinidinequinidine Best TX for Pf malaria; low costBest TX for Pf malaria; low Best TX for Pf malaria; low costcost

Limited R; rapidly acting Limited R; rapidly Limited R; rapidly acting acting

Fairly toxic (cinchonism, cardiac)Fairly toxic (Fairly toxic (cinchonismcinchonism, , cardiac)cardiac)

AmodiaquineAmodiaquineAmodiaquine TX of R Pf malaria TX of R Pf malaria TX of R Pf malaria Low costLow costLow cost Toxicity (bone marrow, liver); R Common Toxicity (bone marrow, Toxicity (bone marrow, liver); R Common liver); R Common

MefloquineMefloquineMefloquine CP against R malaria; not approved for TX in United State

CP against R malaria; not CP against R malaria; not approved for TX in United approved for TX in United StateState

Relatively little R, though increasing; long half-life

Relatively little R, Relatively little R, though increasing; though increasing; long halflong half--lifelife

Moderately toxic (mostly CNS); high cost; R in SE Asia

Moderately toxic (mostly Moderately toxic (mostly CNS); high cost; R in SE CNS); high cost; R in SE AsiaAsia

FansidarFansidarFansidar TX of Pf malaria; no longer recommended for CPTX of Pf malaria; no longer TX of Pf malaria; no longer recommended for CPrecommended for CP

Relatively low cost; long half-lifeRelatively low cost; Relatively low cost; long halflong half--lifelife

Skin toxicity (can be fatal); increasing RSkin toxicity (can be fatal); Skin toxicity (can be fatal); increasing Rincreasing R

PrimaquinePrimaquinePrimaquine Eradication of chronic liver stage Pv,Po malariaEradication of chronic liver Eradication of chronic liver stage stage Pv,PoPv,Po malariamalaria

Only drug for this indicationOnly drug for this Only drug for this indicationindication

Hemolysis with G6Pd deficiency; increasing RHemolysisHemolysis with G6Pd with G6Pd deficiency; increasing Rdeficiency; increasing R

ProgunilProgunilProgunil CP only (often with Chloroquine) CP only (often with CP only (often with ChloroquineChloroquine) )

Low cost; nontoxicLow cost; nontoxicLow cost; nontoxic R commonR commonR common

S-P CombinationsSS--P CombinationsP Combinations CP only (often with Chloroquine)CP only (often with CP only (often with ChloroquineChloroquine))

Low costLow costLow cost R Common; skin rashes R Common; skin rashes R Common; skin rashes

TetracyclineTetracyclineTetracycline Cp; TX of Pf malaria in Combination with quinineCp; TX of Pf malaria in Cp; TX of Pf malaria in Combination with quinineCombination with quinine

Low cost Low cost Low cost Skin and gastrointestinalSkin and gastrointestinalSkin and gastrointestinal


New New antimalarialantimalarial drugsdrugsDrugDrugDrug RoleRoleRole Best Feature(s)Best Best Feature(sFeature(s)) LimitationsLimitationsLimitations

HalofantriineHalofantriineHalofantriine TX of Pf malaria; not approved for CP

TX of Pf malaria; not TX of Pf malaria; not approved for CP approved for CP

Usually effective against R Pf malaria

Usually effective against R Usually effective against R Pf malariaPf malaria

Variable bioavailability, cardiac toxicity

Variable bioavailability, Variable bioavailability, cardiac toxicitycardiac toxicity

Artemisinin and related compounds

ArtemisininArtemisinin and and related compoundsrelated compounds

TX of Pf malariaTX of Pf malariaTX of Pf malaria Rapidly acting; effective against multidrug-R

Rapidly acting; effective Rapidly acting; effective against against multidrugmultidrug--RR

Recurrence after TX fairly common

Recurrence after TX fairly Recurrence after TX fairly commoncommon

AtovaquoneAtovaquoneAtovaquone ? TX of Pf malaria? CP (Probably in

combination with proguanil

? TX of Pf malaria? ? TX of Pf malaria? CP (Probably in CP (Probably in

combination with combination with proguanilproguanil

Limited toxicity Limited toxicity Limited toxicity Limited studies so far show frequent recurrence

after TX

Limited studies so far Limited studies so far show frequent recurrence show frequent recurrence

after TXafter TX

PyronaridinePyronaridinePyronaridine ? TX of malaria ? TX of malaria ? TX of malaria Effective against R strainsEffective against R strainsEffective against R strains Studies limited to dateStudies limited to dateStudies limited to date

DesferrioxamineDesferrioxamineDesferrioxamine ? TX of severe Pf malaria

? TX of severe Pf ? TX of severe Pf malaria malaria

Well tolerated when used for iron overload

Well tolerated when used Well tolerated when used for iron overload for iron overload

Studies limited to date Studies limited to date Studies limited to date

AzithromycinAzithromycinAzithromycin ? CP? CP? CP Limited toxicity Limited toxicity Limited toxicity Studies limited to dateStudies limited to dateStudies limited to date

Other Drugs for Chemotherapy of MalariaOther Drugs for Chemotherapy of MalariaOther Drugs for Chemotherapy of Malaria

Many drugs have been tested for their potential anti malarial effects. Research into newer anti malarialsbeing scanty, such attempts might throw up one or two candidates for use in malaria, however, these drugs are yet to find a place in standard anti malarial regimen. Clindamycin, fluoroquinoloneslike ciprofloxacin and Norfloxacin, azithromycin etc. have been found to be effective against malarial parasites.Atovaquone; Desferrioxamine; Pyronaridine; Piperaquine; WR-288, 605; and 566C80 are drugs undergoing trials.

Many drugs have been tested for Many drugs have been tested for their potential anti malarial effects. their potential anti malarial effects. Research into newer anti Research into newer anti malarialsmalarialsbeing scanty, such attempts might being scanty, such attempts might throw up one or two candidates for throw up one or two candidates for use in malaria, however, these use in malaria, however, these drugs are yet to find a place in drugs are yet to find a place in standard anti malarial regimen. standard anti malarial regimen. ClindamycinClindamycin, , fluoroquinolonesfluoroquinoloneslike ciprofloxacin and like ciprofloxacin and NorfloxacinNorfloxacin, , azithromycinazithromycin etc. etc. have been found to be effective have been found to be effective against malarial parasites.against malarial parasites.AtovaquoneAtovaquone; ; DesferrioxamineDesferrioxamine; ; PyronaridinePyronaridine; ; PiperaquinePiperaquine; ; WRWR--288, 605; and 566C80 288, 605; and 566C80 are are drugs undergoing drugs undergoing trials.trials.

Clindamycin: It acts by inhibiting the protein synthesis by binding to the 50s subunit of ribosomes. It can be used for drug resistant malaria along with quinine at a dose of 10 mg/kg 8 hourly for 5 days. Adverse effects include pseudomembrane colitis and skin rashes. In one study, a cure rate of only 50% was observed. (Hall et al)

ClindamycinClindamycin:: It acts It acts by inhibiting the protein by inhibiting the protein synthesis by binding to synthesis by binding to the 50s subunit of the 50s subunit of ribosomesribosomes. . It can be It can be used for drug resistant used for drug resistant malaria along with malaria along with quinine at a dose of 10 quinine at a dose of 10 mg/kg 8 hourly for 5 mg/kg 8 hourly for 5 days.days. Adverse effects Adverse effects include include pseudomembranepseudomembrane colitis colitis and skin rashes. In one and skin rashes. In one study, a cure rate of only study, a cure rate of only 50% was observed. (Hall 50% was observed. (Hall et al)et al)

Fluoroquinolones:Both ciprofloxacin and norfloxacinhave been found to have anti malarial activity both in vitro and in vivo. However, results are not consistent.

FluoroquinolonesFluoroquinolones::Both Both ciprofloxacin ciprofloxacin and and norfloxacinnorfloxacinhave been found to have been found to have anti malarial have anti malarial activity both in activity both in vitro and in vivo. vitro and in vivo. However, results However, results are not consistent.are not consistent.

Azithromycin: Azithromycinis found to have anti malarial activity and has been found to be useful as a causal prophylactic agent. It was found to be effective at the dose of 300 mg stat, followed by 250 mg daily for 7 days as a prophylactic agent against chloroquine resistant P. falciparum infection.

AzithromycinAzithromycin:: AzithromycinAzithromycinis found to have anti malarial is found to have anti malarial activity and has been found to activity and has been found to be be useful as a causal useful as a causal prophylactic agent.prophylactic agent. It was It was found to be effective at the found to be effective at the dose of 300 mg stat, followed dose of 300 mg stat, followed by 250 mg daily for 7 days as by 250 mg daily for 7 days as a prophylactic agent against a prophylactic agent against chloroquinechloroquine resistant P. resistant P. falciparumfalciparum infectioninfection..

Atovaquone plus Proguanil:A fixed dose combination of atovaquone and proguanilhydrochloride (Malarone™) is now approved for both treatment and prophylaxis of malaria. It is available as 250 mg atovaquone + 100 mg proguanil per tablet for adults and 62.5 mg atovaquone + 25 mg proguanil per tablet for children. It has been shown to be highly efficacious in the treatment of uncomplicated malaria caused by Plasmodium falciparum, including malaria that has been acquired in areas with chloroquine-resistant or multidrug-resistant strains. The daily dose should be taken at the same time each day with food or milk.

AtovaquoneAtovaquone plus plus ProguanilProguanil::A fixed dose combination of A fixed dose combination of atovaquoneatovaquone and and proguanilproguanilhydrochloridehydrochloride ((MalaroneMalarone™™)) is now is now approved for approved for both treatment and both treatment and prophylaxis of malariaprophylaxis of malaria. . It is available It is available as 250 mg as 250 mg atovaquoneatovaquone + 100 mg + 100 mg proguanilproguanil per tablet for adults and per tablet for adults and 62.5 mg 62.5 mg atovaquoneatovaquone + 25 mg + 25 mg proguanilproguanil per tablet for childrenper tablet for children. It . It has been shown to be has been shown to be highly highly efficacious in the treatment of efficacious in the treatment of uncomplicated malaria caused by uncomplicated malaria caused by Plasmodium Plasmodium falciparumfalciparum,, including including malaria that has been acquired in malaria that has been acquired in areas with areas with chloroquinechloroquine--resistant or resistant or multidrugmultidrug--resistant strainsresistant strains. The daily . The daily dose should be taken at the same dose should be taken at the same time each day with food or milk.time each day with food or milk.

Pyronaridine: Structurally, it resembles amodiaquine and has been found to be highly effective against chloroquine resistant strains in China. Piperaquine: Its activity is similar to that of chloroquine. A combination with artimisinin is undergoing studies.WR-288, 605: It is 7.4 times more active than primaquine as a tissue schizonticidal drug. It has lesser toxicity, good oral bio-availability and longer half-life.Lumefantrine is an aryl alcohol related to quinine, mefloquine and halofantrine that is devoid of cardiac toxicity of halofantrine. It is being tried in combination with artemether.

PyronaridinePyronaridine:: Structurally, it Structurally, it resembles resembles amodiaquineamodiaquine and has been and has been found to be found to be highly effective against highly effective against chloroquinechloroquine resistant strainsresistant strains in China. in China. PiperaquinePiperaquine: : Its activity is similar to Its activity is similar to that of that of chloroquinechloroquine.. A combination A combination with with artimisininartimisinin is undergoing studies.is undergoing studies.WRWR--288, 605:288, 605: It is 7.4 times more It is 7.4 times more active than active than primaquineprimaquine as a tissue as a tissue schizonticidalschizonticidal drug. It has lesser drug. It has lesser toxicity, good oral biotoxicity, good oral bio--availability availability and longer halfand longer half--life.life.LumefantrineLumefantrine is an aryl alcohol is an aryl alcohol related to quinine, related to quinine, mefloquinemefloquine and and halofantrinehalofantrine that that is devoid of cardiac is devoid of cardiac toxicity of toxicity of halofantrinehalofantrine. It is being . It is being tried in combination with tried in combination with artemetherartemether..



The Primaquine Questions - Confusions in Primaquine Use In Malaria

To use or not?

Often primaquine is not prescribed for falciparum malaria because it is not needed for attaining a cure of the infection. But it is required to prevent the spread of falciparum infection because unlike in case of vivax malaria, Chloroquine does not sterilize the

gametocytes of falciparum species. Therefore, if primaquine is not used in falciparum malaria, there will be a selective spread of P. falciparum malaria, which may be even resistant to drugs. Therefore, do not forget to use primaquine in P. falciparum malaria-

prevent the spread of P. falciparum, prevent the spread of drug resistant strains! Primaquine is hence a must for both P.vivax and P.falciparum infections.

What is the dose?

0.25mg/kg/day (once a day) for 5 days in P. vivax; 0.75 mg/kg as single dose in P. falciparum.

*5 days or 14 days?

In cases of P. vivax malaria, the National Malaria Eradication Programme (N.M.E.P.) in India recommends Primaquine therapy for 5 days, whereas the standard literature recommends for 14 days. 5 days therapy is adequate in

most cases. In cases of relapse, a 14-day treatment is advisable.

What is the alternative to primaquine?

At present, Primaquine is the only drug available for tissue schizonticidal activity in P. vivaxmalaria and gametocytocidal activity in P. falciparum infection. Therefore, it must be used in both

these infections. Therefore, at present there are no alternatives to primaquine. Newer anti malarials like mefloquine or artemisinin derivatives are NOT substitutes for primaquine!

Is there primaquineresistance?

Although resistance to primaquine has been reported from S. E. Asia and Africa, it is rare. Such cases are managed with a higher dose of primaquine.

Primaquine or ‘parda’?

(Mosquito nets)

In some hospitals, patients with malaria are made to lie inside mosquito nets, with the idea of preventing the spread of the infection to the 'hospital mosquitoes' and hence to other patients.

Often these patients are not administered primaquine. Remember, mosquito nets may not prevent the spread of falciparum malaria, but Primaquine WILL.


GG--6 P D Deficiency6 P D Deficiency--Four most common variants out of 300+ knownFour most common variants out of 300+ known

GdGdBB Normal ActivityNormal ActivityAll World All World

PopulationsPopulations

GdGdAA Normal Activity; Acetic acid substituted for Normal Activity; Acetic acid substituted for asparagineasparagine at at position 126, Guanine for adenine at DNA position376position 126, Guanine for adenine at DNA position376

Africa (most Africa (most common variant)common variant)

GdGdAA--

8 8 -- 20% Normal Activity; 20% Normal Activity; MethionineMethionine for for ValineValine at position 67 at position 67 and Aspartic Acid for and Aspartic Acid for AsparagineAsparagine at position 126, Adenine for at position 126, Adenine for Guanine at position 202 and Guanine for Adenine at position Guanine at position 202 and Guanine for Adenine at position

376376AfricaAfrica

GdGdMedMed < 5% Normal Activity; Phenylalanine for Serine at < 5% Normal Activity; Phenylalanine for Serine at position 188; Thiamine for Cytosine at position 563position 188; Thiamine for Cytosine at position 563

Iran, Iraq, Iran, Iraq, India,India,Pakistan, Greece, Pakistan, Greece,

SardiniaSardinia


PrimaquinePrimaquine Treatment Regimens Treatment Regimens

GG--66--PD NORMAL PD NORMAL 1 tablet* per day x 14 days 1 tablet* per day x 14 days

* * The Indian programme The Indian programme recommends 5 days RT regime to recommends 5 days RT regime to

all all P.vivaxP.vivax cases.cases.

GG--66--PD deficiencyPD deficiency(Mild African form) (Mild African form)

3 tablets per week 3 tablets per week for 8 weeksfor 8 weeks

GG--66--PD deficiencyPD deficiency(More severe (More severe

Mediterranean variety)Mediterranean variety)--Indian strainIndian strain

2 tablets per week for 2 tablets per week for 30 weeks 30 weeks

••1 tablet consists of 26.3 mg 1 tablet consists of 26.3 mg pimaquinepimaquine phosphate, 15 mg phosphate, 15 mg primaquineprimaquine base. base.

••……..So there is no absolute contraindication ! ! ..So there is no absolute contraindication ! !


Potential Vaccines in Malaria.Potential Vaccines in Malaria.

TargetTarget ProtectionProtection

SporozoiteSporozoite antianti--infectioninfection

MerozoiteMerozoite antianti--parasiteparasite

Infected RBCInfected RBC antianti--parasiteparasite

ExoExo--antigensantigens antianti--diseasedisease

Sexual stagesSexual stages antianti--transmissiontransmission

Malaria is a preventable infection that can be fatal if left untMalaria is a preventable infection that can be fatal if left untreated.reated.Currently, you cannot be vaccinated against malaria, but you canCurrently, you cannot be vaccinated against malaria, but you can protect yourselfprotect yourself


Characteristics of thick and thin blood smears Characteristics of thick and thin blood smears Characteristics of thick and thin blood smears

Thick SmearThick Smear Thin SmearThin SmearLysedLysed RBCsRBCs Fixed Fixed RBCsRBCs

Many layersMany layers Single layerSingle layer

Large volumeLarge volume Smaller volumeSmaller volume

Good screening testGood screening test Good species differentiationGood species differentiation

Low density infection can be Low density infection can be detecteddetected

Low density infection can be Low density infection can be missedmissed

Difficult to diagnose speciesDifficult to diagnose species Requires more time to read but Requires more time to read but good for species diagnosis.good for species diagnosis.


MALARIAMALARIA------ THINK BEYOND CLINICAL CURETHINK BEYOND CLINICAL CURE

SOME POINTS TO PONDER FOR PHYSICIANSSOME POINTS TO PONDER FOR PHYSICIANS

ØØ CLINICAL CURE WITH APPROPRIATE BLOOD SCHIZONTICIDALSCLINICAL CURE WITH APPROPRIATE BLOOD SCHIZONTICIDALS

ØØ GAMETOCYTES,WHEN LATER SUCKED BY THE VECTOR GAMETOCYTES,WHEN LATER SUCKED BY THE VECTOR MOSQUITOS,DEVELOP IN THEIR BODY INTO DISEASE CAUSING MOSQUITOS,DEVELOP IN THEIR BODY INTO DISEASE CAUSING SPOROZOITES WHICH ARE TRANSMITTED AGAIN TO THE NEXT HEALTHY SPOROZOITES WHICH ARE TRANSMITTED AGAIN TO THE NEXT HEALTHY PERSON BY THE MOSQUITO BITE PERSON BY THE MOSQUITO BITE ––THUS ANOTHER HUMAN BEING FALLS THUS ANOTHER HUMAN BEING FALLS VICTIM TO THE DEADLY MALARIA .VICTIM TO THE DEADLY MALARIA .

ØØ THIS TRANSMISSION OF MALARIA CAN BE PREVENTED BY THIS TRANSMISSION OF MALARIA CAN BE PREVENTED BY ADMINISTERING GAMETOCYTOIDAL DRUGS LIKE PRIMAQUINE AFTER ADMINISTERING GAMETOCYTOIDAL DRUGS LIKE PRIMAQUINE AFTER CONTROLLING THE ACUTE STAGES OF THE DISEASE .CONTROLLING THE ACUTE STAGES OF THE DISEASE .

ØØ THE PRACTICE OF USING GAMETOCYTOCIDAL DRUGS SHOULD BE THE PRACTICE OF USING GAMETOCYTOCIDAL DRUGS SHOULD BE CONSIDERED AS IMPORTANT AND SHOULD BECOME A PART OF CONSIDERED AS IMPORTANT AND SHOULD BECOME A PART OF STANDARD TREATEMENT STRATEGY WHENEVER A CASE OF STANDARD TREATEMENT STRATEGY WHENEVER A CASE OF P.FALCIPARUM IS ENCOUNTERED.P.FALCIPARUM IS ENCOUNTERED. …………contdcontd


MALARIA---BEYOND CLINICAL CURESOME POINTS TO PONDER FOR PHYSICIANS

CLINICAL CURE WITH APPROPRIATE BLOOD SCHIZONTICIDALS .

GAMETOCYTES,WHEN LATER SUCKED BY THE VECTOR MOSQUITOS,DEVELOP IN THEIR BODY INTO DISEASE CAUSING SPOROZOITES WHICH ARE TRANSMITTED AGAIN TO THE NEXT HEALTHY PERSON BY THE MOSQUITO BITE –THUS ANOTHER HUMAN BEING FALLS VICTIM TO THE DEADLY MALARIA .

THIS TRANSMISSION OF MALARIA CAN BE PREVENTED BY ADMINISTERING GAMETOCYTOIDAL DRUGS LIKE PRIMAQUINE AFTER CONTROLLING THE ACUTE STAGES OF THE DISEASE .

THE PRACTICE OF USING GAMETOCYTOCIDAL DRUGS SHOULD BE CONSIDERED AS IMPORTANT AND SHOULD BECOME A PART OF STANDARD TREATEMENT STRATEGY WHENEVER A CASE OF P.FALCIPARUM IS ENCOUNTERED.

MALARIAMALARIA------BEYOND CLINICAL CUREBEYOND CLINICAL CURESOME POINTS TO PONDER FOR PHYSICIANS SOME POINTS TO PONDER FOR PHYSICIANS

CLINICAL CURE WITH APPROPRIATE BLOOD SCHIZONTICIDALS .CLINICAL CURE WITH APPROPRIATE BLOOD SCHIZONTICIDALS .

GAMETOCYTES,WHEN LATER SUCKED BY THE VECTOR GAMETOCYTES,WHEN LATER SUCKED BY THE VECTOR MOSQUITOS,DEVELOP IN THEIR BODY INTO DISEASE CAUSING MOSQUITOS,DEVELOP IN THEIR BODY INTO DISEASE CAUSING SPOROZOITES WHICH ARE TRANSMITTED AGAIN TO THE NEXT SPOROZOITES WHICH ARE TRANSMITTED AGAIN TO THE NEXT HEALTHY PERSON BY THE MOSQUITO BITE HEALTHY PERSON BY THE MOSQUITO BITE ––THUS ANOTHER HUMAN THUS ANOTHER HUMAN BEING FALLS VICTIM TO THE DEADLY MALARIA .BEING FALLS VICTIM TO THE DEADLY MALARIA .

THIS TRANSMISSION OF MALARIA CAN BE PREVENTED BY THIS TRANSMISSION OF MALARIA CAN BE PREVENTED BY ADMINISTERING GAMETOCYTOIDAL DRUGS LIKE PRIMAQUINE AFTER ADMINISTERING GAMETOCYTOIDAL DRUGS LIKE PRIMAQUINE AFTER CONTROLLING THE ACUTE STAGES OF THE DISEASE .CONTROLLING THE ACUTE STAGES OF THE DISEASE .

THE PRACTICE OF USING GAMETOCYTOCIDAL DRUGS SHOULD BE THE PRACTICE OF USING GAMETOCYTOCIDAL DRUGS SHOULD BE CONSIDERED AS IMPORTANT AND SHOULD BECOME A PART OF CONSIDERED AS IMPORTANT AND SHOULD BECOME A PART OF STANDARD TREATEMENT STRATEGY WHENEVER A CASE OF STANDARD TREATEMENT STRATEGY WHENEVER A CASE OF P.FALCIPARUM IS ENCOUNTERED.P.FALCIPARUM IS ENCOUNTERED.


Control of malaria is a complex chain of measures that often comControl of malaria is a complex chain of measures that often complement one plement one another. The above diagram depicts this control chain: For examanother. The above diagram depicts this control chain: For example, by taking ple, by taking

personal protective measures, personal protective measures, three things can be achieved three things can be achieved -- prevention of prevention of malaria in the given individual, thus reduced parasite load and malaria in the given individual, thus reduced parasite load and reduction in reduction in spread, and by denying blood meal to the mosquito the egg layingspread, and by denying blood meal to the mosquito the egg laying is also is also

hamperedhampered! In the recent years, more emphasis is being laid on early diag! In the recent years, more emphasis is being laid on early diagnosis nosis and treatment, on personal protection especially with insecticidand treatment, on personal protection especially with insecticide treated e treated

bednetsbednets and on biological vector control. By these means, it is intendeand on biological vector control. By these means, it is intended to d to minimiseminimise use of potentially harmful chemical insecticides.use of potentially harmful chemical insecticides.


IT MUST ALWAYS BE REMEMBERED THAT MALARIA IS A LOCAL PHENOMENA AND ITS FOCAL NATURE IS DETERMINED BY

THE FLIGHT RANGE OF THE LOCAL VECTOR(S)POPULATION .

AS LONG AS MALARIA PARASITES REMAIN IN THE HUMAN BODY, IT IS MORE OR LESS PROTECTED FROM THE ENVIRONMENT AND ITS DEVELOPMENT CONTINUES UNABATED EXCEPT FOR THE

INFLUENCE OF THE IMMUNITY OR ADMINISTRATION OF APPRPRIATE ANTI-MALARIA DRUGS .

IT MUST ALWAYS BE REMEMBERED THAT MALARIA IS A IT MUST ALWAYS BE REMEMBERED THAT MALARIA IS A LOCAL PHENOMENALOCAL PHENOMENA AND ITS AND ITS FOCAL NATUREFOCAL NATURE IS DETERMINED BY IS DETERMINED BY

THE THE FLIGHT RANGEFLIGHT RANGE OF THE LOCAL VECTOR(S)POPULATION .OF THE LOCAL VECTOR(S)POPULATION .

AS LONG AS MALARIA PARASITES REMAIN IN THE HUMAN AS LONG AS MALARIA PARASITES REMAIN IN THE HUMAN BODY, IT IS MORE OR LESS PROTECTED FROM THE ENVIRONMENT BODY, IT IS MORE OR LESS PROTECTED FROM THE ENVIRONMENT AND ITS DEVELOPMENT CONTINUES UNABATED AND ITS DEVELOPMENT CONTINUES UNABATED EXCEPT FOR THE EXCEPT FOR THE

INFLUENCEINFLUENCE OF THE IMMUNITY OR ADMINISTRATION OF OF THE IMMUNITY OR ADMINISTRATION OF APPRPRIATE ANTIAPPRPRIATE ANTI--MALARIA DRUGSMALARIA DRUGS ..

THE ENDTHE END

chemotherapy and national drug policy in malaria

Health & Medicine