A COMPARATIVE STUDY ON EFFICACY AND ADVERSE

EFFECTS OF ANTIMALARIALS WITH SPECIAL EMPHASIS ON

PARASITE CLEARANCE TIME

Dr. Tanoy Bose

Co-Authors: Laskar B, Kalita BC, Das S, Dutta A

Department of MedicineAssam Medical College, Dibrugarh

Introduction & Epidemiology• ~ 2 million laboratory confirmed

cases/yr but case incidence is 30 fold or more underestimated. †

• 40-50% is P.falciparum. †

• P. falciparum: Majority parasite (>60%) in NE India: hot spot for proliferation and corridor for spread of drug-resistant malaria to rest of peninsular India. ‡

• NVBDC still depends on Chloroquine to combat malaria ; RESULT: Pf has taken deep roots in malaria endemic regions. §

• Continuation of an outdated drug in Rx of all P.f cases : counterproductive in fighting drug res malaria & containment of Pf. §

Trends of malaria transmission and species composition inthe Sonapur Primary Health Centre, Kamrup district, Assam for the years (1991-2007). Pf, Plasmodium falciparum; Pv, Plasmodium vivax; SPR, slide positivity rate.‡

† NATIONAL ANTI MALARIA DRUG POLICY (2007) ‡ Rolling back malaria is possible. V. Dev, G.C. Doley & A. P. Dash: Indian J Med Res 128, July 2008, pp 82-83

§ Battling malaria iceberg with chloroquine in India Vinod P Sharma :Malaria Journal 2007,6:105

• To study the efficacy of enteral and parenteral antimalarials on parasite density and parasite clearance time

• Their short term

adverse effects in patients admitted with malaria in a teaching hospital of a malaria endemic region.

Objectives:

• A hospital based nonrandomised observational study

• Study Duration: August 2006 to July 2007, Assam Medical College & Hospital

• 165 patients were selected from OPD & Indoor on the basis of slide positivity for Plasmodium falciparum malaria by multiple observers.

• Divided into 3 groups, each group receiving – Chloroquine (Group A) Oral: 25 mg/Kg over 3 days – Quinine (Group B) I.V: 20mg/Kg load X 4hrs f/b 10mg/Kg 8hourly until oral Rx ( Total 7 d)

– Artesunate (Group C) I.V: 2.4mg/Kg f/b 1.2mg/Kg at 12h,24h & daily X 5days

• Clinical assessment and parasitological assessment was done before the initiation of treatment and at day 1, 2, 3, 7, and 14 of treatment and followed up at day 21 and 28

• Resistant cases were treated as per WHO Malaria 2006 Guidelines • Data analysed and interpreted by a single observer

Methodology

Inclusion & Exclusion Criteria:

Inclusion Criteria

Age > 12 years

Axillary Temperature ≥37.5ºC

Uncomplicated malaria

Not receiving any antimalarial prior to hospitalisation

Slide + for P. falciparum

Exclusion Criteria

Slide + Malaria with complications.e.g. ARF, Cerebral Malaria

Coexistent other Systemic illness revealed on Clinical and laboratory evidence

Intake of any antimalarials in past 6 weeks

Pregnancy

Results

0 1 2 3 735.0

35.5

36.0

36.5

37.0

37.5

38.0

38.5

39.0

39.5

40.0

Fever Clearance Time

ChloroquineQuinineArtesunate

Days

Mean T

em

pera

ture

ºC

Significantly early Fever clearance in Artesunate arm (Mean:36hrs) compared to Quinine (Mean: 42hrs) & Chloroquine (Mean: 64hrs)

9% of the patients in Artesunate arm had fever clearance < 24hrs in comparison to none in other arms

0 1 2 3 7 21 280

5000

10000

15000

20000

25000

30000

35000 Parasite Clearance Time

ChloroquineQuinineArtesunate

Days

Num

ber

of

Para

sit

es/c

u.m

m

Level of Parasitemia did not correlate with S/S & biochemical parameters

A parasitemia >15000/cumm of blood was associated with similar S/S & biochemical profile

Artesunate arm showed fastest Parasite clearance rate (100% clearance in <48hrs) followed by Quinine arm (100% clearance in <72hrs) while Chloroquine arm did not show a complete clearance of parasites in 8% of patients suggesting resistance

Tinnitus Nausea/Vomitting Hypoglycemia Hyperbilirubinemia

0%

4%

0% 0%

6.66%

13.32%

6.66%

0.00%0.00%

6.66%

20.00%

Adverse Effects

ChloroquineQuinineArtesunate

Nausea & Vomitting were the commonect adverse effects and was maximum in the Quinine arm (13.32%).

Chloroquine & Artesunate arm were relatively free from adverse effects except for hyperbilirubinemia in artesunate arms

Tinnitus & Hypoglycemia were noticed in 6.66% of patients receiving Quinine

Adverse effects like Hypotension, Arrhythmias, Visual disturbances, Rash were not noted.

• Artesunate arm : Most efficacious with insignificant adverse effects in treating uncomplicated Pf malaria with Median Fever clearance time 36hrs and Parasite clearance time < 48hrs.

• 20% of patients receiving artesunate showed hyperbilirubinemia though liver enzymes were not significantly elevated.

• Quinine arm: Almost as efficacious as Artesunate but associated with side effects. Oral Quinine was poorly tolerated

• Chloroquine arm: Not efficacious and was associated with drug resistance, slower & incomplete parasite clearance

• 8% of patients receiving Chloroquine showed RII level of resistance , 20% cases were recrudescent & total Chloroquine resistant cases were 28%.

Summary of Results & Conclusion

• Artesunate is the most efficacious and least toxic antimalarial and is associated with early recovery & discharge from hospital

• Parenteral Quinine though almost equally efficacious as artesunate, it’s use is associated with important adverse effects and needs close monitoring

• In management of uncomplicated falciparum malaria, the high prevalence of chloroquine resistance should be kept in mind by the clinicians

Take Home Message

THANK YOU

The Department Of Medicine, Assam Medical College,Dibrugarh