sine Derivates IM Versus Quinine IV in Treatment

8/8/2019 sine Derivates IM Versus Quinine IV in Treatment

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Artemether IM versus quinine IV in

treatment of severe malaria inchildren

By Niek Versteegde


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Content

Introduction

Who guidelines

Quinine

Artemether Research

Conclusions

Current practice

Recommendations

References


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0.7-2.7 million death/yr:

>75% children under 5 year

58% of death in 20 poorestcountries

12 000/ year

300-500 million

casus/yearMALARIA in the WORLD :MALARIA in the WORLD :


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Cause of Death in children< 5 years old in Africa

Rank % of all deaths

Malaria 1 20,3Respiratory inf. 2 17,2

Diarrhoea 3 12,3

HIV/AIDS 4 9,0Measles 5 8,4

Low birth weight 6 5,8


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0 1 2 3 4 5 6 7 8 9 10 100

severeuncomplicated

asymptomatic

Prevalence of clinical malaria in Africa

Age/y


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Severe malaria (who)

1. Unrousable coma/ Impaired conciousness2. Severe malaria anemia (Hb 10.000/ul)

3. Repeated convulsions (>3/24 hrs)

4. Hyperparasitemia (>500.000/ul)

5. Pulmonary oedema6. Hypoglycaemia (glc < 2.2 mmol/l)

7. Clinical Shock

8. Renal failure

9. Spontaneous bleeding

10. Haemoglobinuria11. Jaundice

12. Prostrated

13. Hyperpyrexia


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WHO Guidelines

Quinine IV 20 mg/kg loading dose, after that 10mg/kg tds7/7 or 10 mg im, repeat after 4hrs, after that 8hrly untilmalaria is no longer sever. Dilute quinine if given IM

Artemether: 3.2mg/kg loading dose on the first day, afterthat 1.6 mg/kg/day for a minimum of 3 days, until oraltreatment can be taken.

Complete treatment in severe malaria following parenteral

artesunate or artemether administration by giving a fullcourse of artemisinin-based combination therapy or oralquinine to complete 7 days of treatment.


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Quinine Advantages:

well known drug,

possible as singledrug therapy

Easy to switch to oral therapy

Disadvantages:

Complex administration Difficult to get IV acces in children

Loading dose of 20mg/kg

Administration tds

Reported increase in resistance

Practical difficulties in combination with BT or IV fluids

Contraindicated when haematuria Side effects

Gastro-intestinal (vomiting, diarhoea, nausea)

Hypoglycaemia (especially IV)

Tinnitus, vertigo, hypotension, rarely haemolysis


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Artemether

Advantages: Easy administration; IM once daily (first dose at OPD?)

No resistance reported in Africa

Easy to combine with IV fluids and BT

Less side effects,

Disadvantages: Longer hospital stay

Needs an additional course ofSP, quinine or Doxycyclin?

Less experience in severe malaria Costs: one vial artemether of 80mg 3000 Tsh versus one vial

quinine of 300mg 500 Tsh, one tab quinine of 300 mg is 200Tsh


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Artemisinin derivatives versus quinine in treating severe malaria

in children: a systematic review; George PrayGod*1, Albie de Frey2 andMichael Eisenhut3, Published: 17 October 2008

Twelve trials included (1,524 subjects).

No difference in mortality (RR = 0.90, 95% CI 0.73 to 1.12).

The artemisinin derivatives resolved coma faster than quinine (WMD = -4.61, 95% CI: -7.21 to -2.00, fixed effectmodel), when only trials withadequate concealment reviewed not statistical significant

No statistically significant difference in: parasite clearance time,

fever clearance time

incidence of neurological sequelae

28th day cure rate.


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Artemisinin derivatives versus quinine for cerebral malaria in

African children: a systematic review; Bull World Health Organ2009;87:896904 | doi:10.2471/BLT.08.060327

Nine RCTs were included in the analysis, all from Africa. Five had adequate

allocation concealment.

Seven trials compared artemether with quinine (1220 children), twoarteether with quinine (194 children).

No statistically significant difference was found between artemisinin

derivatives and quinine in preventing mortality (relative risk, RR: 0.91; 95%

confidence interval,CI: 0.731.14; I : 0%).

In secondary outcomes measured there were no significant differences.


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Conclusions:

Artemether appears to be as safe and efficientas quinine

Moderate level of evidence;

Many small studies

Quality of studies not adequate

Further research necessary for more firmconclusions.


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Controversies

Efficacy artemether in very severe malaria?

No long term outcomes measured

No research on side-effects, anemia,wellbeing, etc.

Combination therapy?

Additional therapy (SP quinine) necessaryafter artemether?


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Disadvantages of current practice in

management of s. Malaria

Often delayed first gift

No loading dose of quinine

Inadequate continuation of quinine, IV doses notgiven, tablets not given or to late

Inadequate management of convulsions: often noRBG taken, diazepam often not given or given

late, no dextrose for hypos No continuation of adequate therapy in patients

subconscious/vomiting


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Propositions for protocol

In sev. Malaria in children give Artemether in stead of quinine.

Give loading dose at OPD

Give every child that is not eating/drinking adequate a Dextrose 5%

drip to prevent hypolglycaemia (unless crepitations) Prescribe diazepam 0.25mg/kg IV or 0.5mg/kg/PR when convulsing

Phenobarbital: WHO guidelines 15 mg/kg loading dose ?

Always do BS! if NPS or low count < 10mps: consider meningitis +LP

If signs of meningitis; Neckstiff+ and/or Kernig sign + or in doubtabout it: do LP

If in doubt and not able to do LP at that moment Start cephtriaxon100mg /kg Schedule LP for later,or ask for help


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Questions?


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Referrences

Harrisons Principles of internal medicine 16thedition

Farmacotherapeutisch kompas

Who pocket book of hospital care for children

Artemisinin derivatives versus quinine in treatingsevere malaria in children: a systematic review; GeorgePrayGod*1, Albie de Frey2 and Michael Eisenhut3, Published:17 October 2008

Artemisinin derivatives versus quinine for cerebralmalaria in African children: a systematic review; BullWorld Health Organ 2009;87:896904 |doi:10.2471/BLT.08.060327

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sine Derivates IM Versus Quinine IV in Treatment