Transcript Management of Malaria – Dr M Ridwanur Rahman

Management of Malaria
Dr M Ridwanur Rahman
Professor (Medicine), ShSMC, Dhaka
Member, Malaria Research Group, Ctg
THE BURDEN OF MALARIA
>100 countries in the world are malarious
 >2 billion people are exposed to the risk of
malaria infection annually.
 Residents of non-endemic areas also have,
Travel malaria
Airport malaria

High Risk Groups
 Young children (6 months - 5 years)
 -Pregnant women (primigravids)
 -Non-immune migrants (Military personnel,
expatriates, tourists, refugees).
High Risk Malaria Areas in Bangladesh
Case Load: Malaria in Bangladesh,
1963 – 1998
Clinical Malaria - Treatment
Non falciparum malaria-
Uncomplicated
Uncomplicated Malaria
(falciparum)
Severe (Complicated) Malaria
Malaria Case Fatality Rates
 Severe malaria
10-40%
 Moderately severe malaria 3%
 Uncomplicated malaria
<1%
Relationship between life cycle & clinical features
Cycle/feature
Vivax/ovale
Malariae
Falciparum
Incubation
8-25 days
15-30 days
8-25 days
Asexual cycle
48 hrs,
synchronus
72 hrs,
synchronus
<48 hrs,
asynchronus
Periodicity of
fever
Tertian
Quartan
Aperiodic
Exoerythrocytic
Persist as
hypnozoites
None
None
Delayed onset
common
rare
Rare
Relapses
Common upto
2 years
Recrudescence
many years
Recrudescence
upto 1 year
Clinical Features
 Fever- classically intermittent & periodic
 3 stages described
 Asymptomatic apyrexial intervals
 Malaise, Headache, bodyache & vomiting
 Cough & mild diarrhoea- children
 Jaundice relatively common- falciparum
 No specific physical sign
 Liver & spleen- enlarge & tender
 Anaemia frequent in falciparum
D/D in uncomplicated disease
 Flue like illness’
 Enteric fevers
 RTI’s
 UTI
 Dengue
 SSTI
 Others
Diagnosis
 High index of suspicion- H/O chance
of contact, absence of
symptom/signs of other disease,
characteristic C/F
 Blood slide examination
 Dipstick Tests
 Other tests- to exclude other D/D,
e.g., urine R/M/E, CBC, CXR etc.
Classification of antimalarial drugs
based on chemical structures
 4-aminoquinolines e.g. chloroquine, hydroxychloroquine,
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amodiaquine
8-aminoquinolnes e.g. primaquine
2,4-diaminopyrimidine e.g. pyrimethamine
Arylaminoalcohols e.g. quinine, mefloquine, lumefantrine
Acridine derivatives e.g. quinacrine, mepacrine, pyronaridine
Biguanides e.g. chloroguanide, chloroproguanil
Suphonamides and sulphones e.g. sulphadoxine and dapsone
respectively
Phenanthrene methanols e.g. halofanthrine
Naphthoquinones e.g. atovaquone
Artemisinins e.g. dihydroartemisinin, artesunate, artemether,
arteether, e.t.c.
FACTORS THAT GOVERN
CHOICE OF DRUGS
 Parasite species
 Local Level of resistance to drugs
 Patient’s general health and medical
history.
 Availability of medication in the country
of prescription.
 Intended use (prophylactic or
therapeutic).
Drug resistant Malaria
 Resistance is the ability of an
organism to survive or multiply
despite presence of the drug –
exhibited by falciparum only
 CQ, S/P resistance in Bangladesh
 May have reduced sensitivity to Q & M
 Bangladesh is a multi-drug resistant
falciparum area
Factors aiding Resistance in
malaria parasites.
 Indiscriminate drug use
 Sub-optimal dosages
 Non compliance with treatment
course
 Low quality drugs
 Fake and substandard drugs
WHO Treatment Guidelines
 Artemisinin-based Combination Therapies
(ACTs) should be first line treatment for
falciparum malaria everywhere.
 This should ideally be formulated in fixed
dose combinations when possible.
 Therapeutic options for ACT
-Artesunate-SP
-Artemether-lumefantrine
-Artesunate-amodiaquine
-Artesunate-mefloquine
-Dihydroartemisinin-piperaquine
What are Artemisinins ?
Artemisinin derivatives
Dihydroartemisin
Qinghaosu
("ching-how-soo")
Ethyl Ether
Methyl Ether
Arteether
Artemether
Hemisuccinate
Artesunate
First demonstration project
in Thailand
Treatment efficacy at Thai-Burmese border
Cured (%)
100
Mefloquine +
artesunate
80
Mefloquine25
Mefloquine15
60
19
Year
99
19
98
19
97
19
96
19
95
19
94
19
93
19
92
19
91
19
90
19
85
-8
6
40
Artemisinin-based combination
therapy in uncomplicated malaria
Widespread use of
1st line Rx with
Artemisinin-based
Combination
Therapy
Improve clinical cure rates
Delay emergence of
resistance
Reduce transmission
Cost effective
Treatment of Uncomplicated
Malaria
 Non-Falciparum-
- Chloroquine 25 mg/kg over 3
days, (Tab 4-4-2, adults)
- & primaquine 15 mg/d, 14 days
 Falciparum- ACT
Co-artem - 6 doses
2nd line- Alternative ACT, Q7T7 or
Q7D7
What to give in pregnancy ?
 In 1st trimester

Quinine + Clindamycin 7 days
 In 2nd and 3rd trimesters

Any ACT combination as per rec. or

Artesunate + Clindamycin 7 days or

Quinine + Clindamycin 7 days
 Lactating women same ACT
CLASSIFICATION OF THERAPEUTIC
RESPONSE (WHO 2004)
3 Categories
 Early treatment failure (ETF)
 Late treatment failure (LTF)


Late clinical failure
Late parasitological failure
 Adequate clinical and parasitological
response (ACPR)
Severe & Complicated Malaria
(SCM)
 Falciparum malaria
 Children, pregnant & short term
travel/resident – endemic zones
 Severe symptoms
 Life threatening in the absence
of early effective treatment
 Medical emergency
Table-1 Types of Severe Manifestations (n=829)
Type SCM (Major)
Full
Recovery
Death
N (%, CFR)
Others 2
Total
N (%)
CNS Manifestations
304
39 (31)
19
362 (44)
36 (27)
10
132 (16)
2 (1)
8
195 (24)
1 (3)
1
35 (4)
Unrousable Coma 86
Impaired Consciousness
185
Convulsion 33
Severe Prostation
193
0
4
197 (24)
Hyper-parasitaemia
172
0
6
178 (22)
Severe Anamia
51
0
16
67 (8)
Hyperpyrexia
14
1 (7)
0
15 (2)
Others
7
0
3
10
Total n (row%)
741 (89)
40 (4.8)
48 (6)
829
SCM – Other Manifestations
 Acute renal failure
 Pulmonary Oedema
 Haemoglobinuria
 Hypoglycaemia
 DIC
 Jaundice
 Multi-organ involvement/failure
May occur singly, often in combination
Management (SCM)
• Medical Emergency
• Appropriate anti-parasitic
Treatment
• Crucial General Management
• Identification & management
of complications
Treatment of severe falciparum
malaria
Any of the following antimalarial
medicines are recommended
– Artesunate i.v. or i.m
– artemether i.m.
– quinine (i.v. infusion or i.m. injection).
Full course of ACT or quinine +
clindamycin or doxycycline when
patient can tolerate oral treatment
Artemisinins parenteral
 αβ Arteether – 150 mg (2ml) i.m od x 3
days or 3 mg/kg od i.m. x 3 days
 Artesunate 2.4 mg/kg i.v. or i.m. given on
admission (time = 0), then at 12 h and 24 h,
then once a day
 Artemether 3.2 mg/kg i.m. given on
admission then 1.6 mg/kg per day is an
acceptable alternative to quinine i.v
infusions
 Rectal artemisinins are not as effective
Quinine parenteral
 A loading dose of quinine of 20 mg
salt/kg bw. 10 mg/kg 8th hrly i.v infusion
 Rate-controlled i.v. infusion is the
preferred route of quinine admin.
 If this cannot be given safely, then i.m.
injection is a satisfactory alternative.
 Rectal admin. is not effective
 Quinidine can substitute quinine
Quinine vs Artemesinin’s
• Artemesinins are more effective than
Quinine in terms of survival (MRG,
contributed)
• No significant difference in coma resolution
time & fever clearance time
• Parasite clearance time faster with A’s
• Hypoglycaemia & cardiotoxicity less A’s
• ? Uterine contractions more with Q’s
• ? Neurologic sequelae more with A’s
(animals)
Cerebral Malaria – D/D
 Meningitis
 Encephalitis
 Sepsis
 Fever in CNS Disease
 Fever in Organ failure
 Typhoid encephalopathy
 Metabolic/Toxic encephalopathy
Severe Anaemia
• More in children & pregnant
population
• Transfuse if Hb <6.0 g/dl
• Fresh whole blood or packed cells
• Include the transfusion volume in
I/O calculation
• Use frusemide if volume over load
Acute Renal Failure
•
•
•
•
Continuous Catheter
Correct dehydration
Use bolus frusemide 20-40 mg IV
Monitor hourly urine output, if <17 ml/hr
established ARF
• Control fluid input if established ARF
• Referral to renal replacement facility
• Pt. Unlikely to die if dialysis facility
available
Hypoglycaemia
• Frequent in young children, pregnant
women & during quinine Rx
• Intervened on suspicion- most important
being deterioration of consciousness &
convulsion
• Bolus 25% glucose 50 cc
• Follow with IV infusion of 5%/10%
glucose
• Continue monitoring for recurrence
Metabolic Acidosis
•
•
•
•
Look for dehydration & hypovolaemia
Isotonic IV infusion, avoid fluid overload
Monitor BP, urine volume & JVP
Improve oxygenation by
- clearing airway
- oxygen inhalation
- support ventilation, if necessary
Pulmonary Oedema
• Very serious, mortality >50%
• Frequent in ARF, pregnancy, severe
anaemia, & at extremes of ages
• Prop up position & oxygen inhalation
• Stop IV fluid & give IV frusemide (40-200
mg)
• Sequential torniquette application
• Haemofiltration
• Mechanical ventilation
• Withdraw blood by venesection
Circulatory Collapse
• Often associated with gm –ve septicaemia
• Common sites- lung, urinary tract,
meningitis, IV lines & injection sites
• Take blood culture, start broad-spectrum
antibiotics (Amoxy + Genta)
• Maintain adequate hydration & output
• Dopamine may be given
Spontaneous bleeding & DIC
• Spontaneous bleeding from DIC is
uncommon but serious complication
• Thrombocytopenia is common but rarely
causes bleeding
• Transfuse fresh blood, clotting factors or
platelets as required
• If PT or PTT prolonged, Inj. Vit. K 10 mg
may be given
Haemoglobinuria
• G6PD deficiency or malaria itself- not
quinine
• Continue appropriate antimalarial if
parasitaemia present
• Transfuse fresh whole blood to Hct >20%
• Monitor JVP/CVP to avoid fluid overload
& hypovolaemia
• Give frusemide 20 mg IV
• Monitor renal function & consider dialysis
if required
Nursing Care
• As important as anti-parasitic Rx
• Meticulous nursing care to
- maintain clear airway
- prevent aspiration pneumonia
- prevent pressure sores
• Careful intake-output chart
• Rate of infusion checked frequently
• Temperature >1020F reduced by tepid sponging &
fanning
• Change in level of consciousness, behaviour &
occurrence of convulsion reported
SCM Management – Common
errors
 Misjudgement of severity
 Delay in starting treatment
 Failure to provide nursing care
 Inappropriate rate of infusion
 Delay in correcting hypoglycaemia
 Failure to control convulsions
 Unnecessary continuation of treatment
 Failure to evaluate con-comitant
conditions
Prevention of Malaria death
 Pre-hospital treatment
- IM Quinine
- Artesunate Suppository (MRG
received BMJ group award for Best
Research Paper of the Year 2010)
 Chemoprophylaxis / IPT
 Malaria Vaccine
DRUGS FOR
CHEMOPROPHYLAXIS
 Pyrimethamine – Limited efficacy
 Proguanil – 200mg daily- Limited efficacy
 Doxycycline – Travelers 200mg daily.

Not in children or pregnant women
 Malarone (Atovaquone/proguanil) –

very effective, good safety margin but expensive ($32 – 35
USD/dose)
 Mefloquine – 250mg weekly

(T1/2 too long, neuro-psychiatric AE)
 Chloroquine/Amodiaquine
 Not recommended as it is used in Rx
 Resistance emerged
 Bone marrow suppression with amodiaquine
Conclusion
 Malaria has no characteristic
clinical feature
 High index of suspicion is the key
 Early diagnosis & Prompt &
appropriate treatment (EDPT) – 1st
contact
 Death is avoidable with early
effective treatment & meticulous
followup