role of act,s & who guidlines for the treatment of malaria

Malaria Today

Global Malaria Action Plan

WHO Guidelines forThe Treatment of Malaria

World Malaria Report 2008

WORLD MALARIA REPORT 2008

Persistent burden of malaria have become a familiar

part of discussions in the global public health forum 3 billion people at risk of infection in 109

malarious countries and territories and around 250 million cases annually leading to approximately

1 million deaths In 2004 Plasmodium falciparum was among the leading

causes of death worldwide from a single infectious agent (1)

1Global burden of disease 2004 update Geneva World Health Organization 2008 (wwwwhointhealthinfobodestimatesenindexhtml)

Population at riskThe 109 countries and territories classified as endemic

The four groups describe the transition from control to eliminationMalaria-free countries and malaria-endemic countries in phases of control pre-elimination elimination and prevention of reintroduction end 2007

Source World Malaria Report 2008 Geneva World Health Organization 2008 2006 data

Burden of Malaria in Pakistan

Malaria has been a persistent problem in Pakistan There

were an estimated 15 million malaria episodes in 2006 Most cases occur between July and November About 30 are due to P falciparum

bullWORLD MALARIA REPORT 2008

EPIDEMIOLOGICAL PROFILE PAKISTANPopulation (000) 2006

bull All age groups 160 943bull lt 5 years 19 012 12bull gt 5 years 141 931 88

Population by malaria endemicity (000) 2006 bull High transmission 1048618 11000 11 422 7bull Low transmission (0ndash11000) 149 521 93bull Malaria-free (0 cases) 0 0bull Rural population 104 222 65

Vector and parasite profile

bull Major Anopheles species bull culicifacies stephensi


Policies Strategies for Malaria Control

The government of every country affected by malaria has a national malaria control policy covering prevention and case-management

Diagnosis and treatment of malaria including preventive treatmentThe objectives of an anti-malarial treatment policy are to Ensure rapid cure of the infection Reduce morbidity and mortality including malaria-related anemia Prevent the progression of uncomplicated malaria into severe and potentially fatal disease Reduce the impact of malaria infection on the fetus during pregnancy Reduce the reservoir of infection Prevent the emergence and spread of drug resistance Prevent malaria in travelers

Malaria Prevention Through Mosquito Control

The main objective of malaria vector control is to reducesignificantly the incidence and prevalence of both parasite infection and clinical malaria

There are two main approaches to malaria prevention by mosquito control-

1The use of insecticide-treated nets (ITNs)

2Indoor residual spraying (IRS)

Antimalarial Drug Resistance

A key factor contributing to the increasing malaria mortality rate is the widespread resistance of P falciparum to conventional antimalarial drugs such as

Chloroquine Sulphadoxine + Pyrimethamine (SP) Amodiaquine

Multi-drug resistant Pfalciparum malaria is widely prevalent in Southeast Asia and some Amazonian regions of South America

South-East Asia has the most drug resistant malaria parasites in the world12

1- WongsrichanalaiC et al (2002) Epidemiology of drug-resistant malaria The Lancet Infectious Diseases 2(4) April 209-18

2- KidsonC et al (2000) The malaria cauldron of Southeast Asia conflicting strategies of contiguous nation states Parassitologia 42 (1-2) June 101-110

WHO Recommendations for the Clinical diagnosis

WHO Guidelines for the treatment of malaria 2006 page 8

In general settings where the risk of malaria is low clinical diagnosis of uncomplicated malaria should be based on-

The degree of exposure to malaria History of fever in the previous 3 days with no features of other severe diseases

In settings where the risk of malaria is high clinical diagnosis should be based on-

History of fever in the previous 24 h the presence of anaemia for which pallor of the palms appears to be the most reliable sign in young children

All uncomplicated P falciparum infections should be treated with an ACTs (Artemisinin - based combination therapy)1

Four ACTs are currently recommended for use 1- Artemether - Lumefantrine2- Artesunate - Amodiaquine3- Artesunate - Mefloquine4- Artesunate ndash Sulfadoxine - pyrimethamine

Severe malaria should be treated parenterally with either an artemisinin derivative or quinine until the patient can swallow when a complete course of ACT must be administered

(The choice of the ACT should be based on the efficacy of the partner medicine in the country or area of intended deployment)

WHO Recommendations for the treatment of malaria


The aim of treatment is to fight an established parasite infection andincludes Elimination of the parasites supportive measures to overcome morbidity associated with infection monitoring - to ensure early diagnosis and treatment of complications

that can lead to death within hours

The choice of an antimalarial depends on a variety of factors including Parasite type 1048618Level of drug resistance Patientrsquos general health and medical history Availability of medications in the country of prescription Country policy and guidelines Intended use (prophylactic or therapeutic)

Treating Malaria amp The Role of Drugs

Artemisinin Derivatives (ACTrsquos)Over the past decade a new group of antimalarial ndash the Artemisinin Compounds especially Artesunate artemether and dihydroartemisinin ndashhave been deployed on an increasingly large scale

These produce a rapid therapeutic response are active against multi-drug resistant P falciparum malaria are well tolerated by patients and reduce gametocyte carriage

To date no parasite resistance to these compounds has been detected Studies in Southeast Asia have shown that combinations of artemisinin compounds with certain other antimalarial produce high cure rates injust 3 days of treatment12

1Lefegravevre G Looareesuwan S Treeprasertsuk S et al A clinical and pharmacokinetic trial of six doses of artemether lumefantrine for multidrug-resistant Plasmodium falciparum malaria in Thailand Am J Trop Med Hyg 2001 64 247-256

2van Vugt M Wilairatana P Gemperli B et al Efficacy of six doses of artemether lumefantrine (benflumetol) in multidrugresistant Plasmodium falciparum malaria Am J Trop Med Hyg1999 60(6) 936-942

Artemisinin Derivatives (ACTrsquos) Conthelliphellip

Artemisinin is a sesquiterpene lactone containing a bridged endoperoxide

It has- Two main lipophilic derivatives artemether and arteether A lesser hydrophilic derivative artesunate A major active metabolite in vivo dihydroartemisinin

The artemisinin derivatives (artesunate dihydroartemisinin artemether or

arteether) are fast acting and potent antimalarial that offer an important

alternative to current treatments

Complying with need of time and recommendations of

WHO Tabros Pharma proudly presents

Co - Misomal is a new safe and effective fixed dose combination antimalrial therapy of artemether-lumefantrine that provides an important addition to the armory against malaria

Rationale

Artemether + Lumefentrine - A highly effective fixed combination Artemether (20 mg) a derivative of artemisinin and lumefantrine (120

mg) a highly lipophilic aryl amino alcohol

Lumefantrine has a much longer elimination half-life (several days) than artemether

With a low recrudescence rate the complementary properties of artemether with its fast onset of action

and Lumefantrine with its long duration of action and high cure rate result in a highly effective combination

Artemether + Lumefentrine overview of Product Characteristics Highly effective against acute uncomplicated malaria caused by P falciparum in areas of multi-drug resistance Eliminates parasites and symptoms significantly faster than most

current antimalarials12

Is rapidly gametocytocidal helping to reduce transmission Achieves high cure rates Well tolerated particularly when compared to most established

antimalarials3

An easy-to-use fixed-dose combination treatment ~ simplifies compliance

Ref1 van Agtmael M Bouchaud O Malvy D et al The comparative efficacy and tolerability of CGP 56697 (artemether +lumefantrine) versus halofantrine in the treatment of uncomplicated falciparum malaria in travellers returning from the tropics to The Netherlands and France Int J Antimicrob Agents 1999 12 159-1692 Kshirsagar NA Gogtay NJ Moorthy NS et al A randomized double-blind parallel-group comparative safety and efficacy trial of oral co-artemether versus oral chloroquine in the treatment of acute uncomplicated Plasmodium falciparum malaria in adults in India Am J Trop Med Hyg 200062 402-4083 van Vugt M Looareesuwan S Wilairatana P et al Artemether-lumefantrine for the treatment of multidrug-resistant falciparum malaria Trans R Soc Trop Med Hyg 2000 94 545-548

IndicationsArtemether + lumefentrine is indicated for the Treatment

of uncomplicated infections due to P falciparum or mixed

infections including P Falciparum in adults and children

Artemether + lumefentrine is Not Indicated for prophylaxis or for treating severe malaria including cerebral malaria pulmonary edema or renal failure because treatment of severe malaria requires Injectable medication

Efficacy of Artemether + Lumefentrine 28-day cure rates in a multi-drug resistant area with 6-dose

Artemether + Lumefentrine

One of these (van Vugt et al 1999) was a doseoptimisation study forcoartemether in multidrugresistant areas1The 4-dose regimen was compared with two 6-dose regimens (givenover either 60or 96 hours)

1van Vugt M Wilairatana P Gemperli B et al Efficacy of six doses of artemether-lumefantrine (benflumetol) in multidrugresistant Plasmodium falciparum malaria Am J Trop Med Hyg1999 60(6) 936-942

Co-Artemether 4 doses Co-Artemether 6 doses 60 hours Co-Artemether 6 doses 95 hours Mefloquine + Artesunate

Overview of Cure Rates in adults and Adolescents 28-day parasitological cure rates by treatment pooled studies

evaluable population PCR-correctedThe following graphic provides an overview of 28-day cure rates for co-artemether

and other antimalarials based on pooled results from evaluable patients gt12 years

of age

Comparator

Patient number to small

in the Evaluation population

Fast Parasite Elimination in P falciparum Malaria

Median percentage parasite reduction at 24 hours was significantly better (plt0001) for patients receiving co-artemether than for tested comparators

Comparator

Parasite Clearance in Infants and Childrenstudy on infants and small children in sub-Saharan Africa (Kenya Nigeria

and Tanzania) with the 6-dose regimen of co-artemether demonstrated

that overall170305 (557) of patients achieved clearance within 24

hours and 302307 (984) within 48 hours

Prompt Reduction in Fever Fever clearance in infants and childrenIn African children fever clearance (and hence symptomatic improvement)

occurred significantly faster with co-artemether than with

sulphadoxine+ pyrimethamine (SP) African children with fever gt375degC

von Seidlein L Bojang K Jones P et al A randomized controlled trial of artemether benflumetol a new antimalarial and pyrimethaminesulfadoxine in the treatment of uncomplicated falciparum malaria in African children Am J Trop Med Hyg 1998 58(5) 638-644

Co-Artemether (n=144) Sulphadoxine + pyrimethamine (n=143)

Fever Clearance in Adults and Adolescents

Fever clearance times pooled studies

Comparator

Gametocyte Clearance in Infants and Children

Rapid gametocyte clearance 6-dose regimen

0-3 days Day 7 Day 14

Gametocyte Clearance in Adults and Adolescents

Proportion of patients with gametocytes by Day 28 pooled studies

Comparator

Safety amp Tolerability

Dosage amp Administration

Body weight in kg

(age in years)

No of tablets at approximate timing of dosing

0 Hrs 8 Hrs 24 Hrs 36 Hrs 48 Hrs 60 Hrs

5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)

No of tablets at Approximate timing of dosing


15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml

75 Kg 10ml 10ml 10ml

10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk


EPIDEMIOLOGICAL PROFILE PAKISTAN




Slide 9


Slide 11

Slide 12


Artemisinin Derivatives (ACTrsquos)


Rationale

Artemether + Lumefentrine - A highly effective fixed combination

Artemether + Lumefentrine overview of Product Characteristics

Indications

Efficacy of Artemether + Lumefentrine

Overview of Cure Rates in adults and Adolescents


Parasite Clearance in Infants and Children

Prompt Reduction in Fever






Slide 31

Slide 32

Slide 33

Slide 34


Persistent burden of malaria have become a familiar

part of discussions in the global public health forum 3 billion people at risk of infection in 109

malarious countries and territories and around 250 million cases annually leading to approximately

1 million deaths In 2004 Plasmodium falciparum was among the leading

causes of death worldwide from a single infectious agent (1)

1Global burden of disease 2004 update Geneva World Health Organization 2008 (wwwwhointhealthinfobodestimatesenindexhtml)



























































Rationale









antimalarials3















of age

Comparator





Comparator












Comparator






Comparator



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34



























































Rationale









antimalarials3















of age

Comparator





Comparator












Comparator






Comparator



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34









antimalarials3















of age

Comparator





Comparator












Comparator






Comparator



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34













of age

Comparator





Comparator












Comparator






Comparator



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34



Comparator












Comparator






Comparator



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34












Comparator






Comparator



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34






Comparator



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34



Body weight in kg

(age in years)



5-14 (lt 3) 1 1 1 1 1 1

15-24 (ge 3ndash8) 2 2 2 2 2 225-34 (ge9 ndash14) 3 3 3 3 3 3

gt 34 ( gt1 4) 4 4 4 4 4 4


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34


Body weight in kg

(age in years)



15-24 (ge 3ndash8) 1 1 1 1 1 1

25-34 (ge9 ndash14) 112 112 112 112 112 112

gt 34 ( gt1 4) 2 2 2 2 2 2


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34


DOSAGE SCHEDULE

BODY WEIGHT

DAY 1 DAY 2 DAY3

5Kg 7 ml 7 ml 7ml


10 Kg 14 ml 14 ml 14 ml

15 Kg 20 ml 20 ml 20 ml

Slide 1


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34


Population at risk






Slide 9


Slide 11

Slide 12




Rationale



Indications











Slide 31

Slide 32

Slide 33

Slide 34

role of act,s & who guidlines for the treatment of malaria

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