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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