Dr. Ankit Gajjar is a critical care physician at Asutosh Hospital. The document discusses malaria, including what causes it, the species that cause malaria in humans, epidemiology in India, pathophysiology, clinical features, diagnosis, treatment for uncomplicated and severe cases of P. falciparum and other species, treatment in specific populations, monitoring and follow up, relapse vs recrudescence, and various artemisinin-based combination therapies.

1. DR ANKIT GAJJAR
MD, IDCCM, IFCCM, EDIC
CRITICAL CARE PHYSICIAN
DR ANKIT GAJJAR
MD, IDCCM, IFCCM, EDIC
ASUTOSH HOSPITAL
CRITICAL CARE PHYSICIAN

2. What causes Malaria
• Malaria is caused by a parasite called
Plasmodium, which is transmitted via the bites of
infected mosquitoes. In the human body, the
parasites multiply in the liver, and then infect red
blood cells.

3. • 4 species of Plasmodium were known to cause malaria
in humans:
P.falciparum,
P.vivax,
P.malariae,
P.ovale

4. Epidemiology of malaria in India
Season: most common in July-November (monsoon)
Definitive host: Anopheles mosquito
Intermediate host: Human
Rarely transfusion related
Type Incubation period
P vivax 8-17 days (14days)
P falciparum 9-14 days (12 days)
P malariae 18-40 days (28 days)
P ovale 16-18 days (17 days)

5. Pathophysiology

6. P. VIVAX causes BENIGN TERTIAN MALARIA
- Benign because it’s rarely fatal
- Tertian as it’s causes fever every 3rd day (48 hr)
- Relapse is a problem
P. FALCIPARUM causes MALIGNANT TERTIAN MALARIA
- Malignant because it’s very fatal
- Tertian as it’s causes fever every 3rd day (48 hr)
- Infected RBCs forms clusters called ROSSETS, Such ROSSETS blocks end
organ capillaries causes Renal failure & cerebral malaria

7. Clinical Features

8. Clinical Features
• Prodromal symptoms
• Headache, photophobia, muscle ache and pain, anorexia and
vomiting
• Cold stage
• Sudden shaking chills or rigor, pale and cyanotic
• 10-15 min
• Hot stage
• Flushed, agitated, restless, disoriented, delirious
• Severe frontal headache, pain in limbs and back
• 2-4 hrs
• Sweating
• Profuse sweating weak and exhausted
• Several hrs

9. DIFFERENTIAL DIAGNOSIS
• Dengue fever
• leptospirosis
• Typhoid fever
• Scrub typhus
• Severe bacterial sepsis

10. WARNING SIGNS

11. Severe complicated malaria
1. Confusion, drowsiness, severe weakness or
continuous high grade fever
2. Hyperparasitemia (P. falciparum > 10% )
3. Impaired consciousness
4. Hypoglycemia
5. Multiple seizures
6. Respiratory distress
7. Pulmonary edema (HYPOXIA)
8. Jaundice
9. Hemoglobinuria (Red or Black Urine)
10. Abnormal bleeding
11. Severe anemia
12. Circulatory collapse

12. Diagnosis of malaria
- Clinical diagnosis
• Fever or unexplained systemic illness
• History of travel from endemic area with previous
year, think about malaria until proven otherwise
- Blood film
• Can take any time (or at the height of fever)
• 3 consecutive days
• Giemsa-stainedThick film andThinfilm

13. Thick film & Thinfilm
• Thick film for MP positive or not
• Thick film facilitates the diagnosis of low level
Parasitemia
• Thin film is essential
• to confirm the diagnosis,
• to identify the species of parasite, &
• to quantify the parasite load by counting the
% of infected RBCs

14. - Rapid DiagnosisTests (RDT) by ICT
Rapid diagnosis for falciparum
• Parasight-F test based upon HRP 2 (Histidine rich
protein 2)
Rapid diagnosis for falciparum and vivax
• LDH coted OptiMAL test kits
• Test took only 5 min
• Sensitivity 100%, specificity 96%
• Importance of ICT
• Rapid Dx
• Can differentiate falciparum and vivax
• Suitable for microscopists less experienced in
examining blood films
• Can detect up to 14 days

16. 1. Treatment of of malaria caused by p.vivax, p. ovale or p. malariae.
CHLOROQUINE
(150 mg base/tab) 25 mg base/kg
divided over 3 days
PRIMAQUINE
(7.5 mg base/tab)
Day 1 Day 2 Day 3
Start concurrently with CHLOROQUINE 0.5
mg base/kg Q24H for 2 weeks
Take with food
Check G6PD status before start primaquine
In mild-to-moderate G6PD deficiency,
primaquine 0.75 mg base/kg body weight
given once a week for 8 weeks.
In severe G6PD deficiency, primaquine is
contraindicated and should not be used.
10mg
base/kg
stat,
then
5mg
base/kg
5mg
base/kg
Q24H
5mg
base/kg
Q24H
1 tab of chloroquine phosphate 250mg equivalent to 150mg base. Calculation of dose for
chloroquine is based on BASE, not SALT form. 1 tab of primaquine phosphate contains
7.5mg base.
For complicated, resistance or treatment failure cases Artimisine based therapy
should be use

17. 2. Treatment of uncomplicated p.falciparum
Preferred regime Alternative regime
Artemether plus lumefantrine(Riamet)
(1 tab: 20mg artemether/120mg lumefantrine)
Quinine sulphate (300mg/tab)
Weight
Group
Day 1 Day 2 Day3 Day 1-7: Quinine 10mg salt/kg PO
Q8H
Plus
*Doxycycline (3.5mg/kg once a day)
OR
*Clindamycin (10mg/kg twice a day)
*Any of these combinations should be
given for 7 days.
Doxycycline: Children>8yr
Clindamycin: Children<8yr
5-14kg 1 tab stat
then 8hr later
1 tab Q12H 1 tab
Q12H
15-24kg 2 tab stat
then 8hr later
2 tab Q12H 2 tab
Q12H
25-34kg 3 tab stat
then 8hr later
3 tab Q12H 3 tab
Q12H
>34kg 4 tab stat
then 8hr later
4 tab Q12H 4 tab
Q12H
Take immediately after a meal or drink containing at
least 1.2g fat to enhance lumefantrine absorption.
Add primaquine 0.75mg base salt/kg single dose if gametocyte is present at any time during
treatment.

18. Artemether + Lumefantrine
• Total dose of 5-24 mg/kgArtemether+
29-144 mg/kg Lumefantrine
• Recommended dosage regimen – twice a day for 6 days
(total 6 doses)
• 1st two doses should be given 8hrs apartideally.
• Advantage of this ACT is that lumefantrine is not available
as monotherapy and has never been used as alone for
malaria treatment
• Absorption of Lumefantrine is enhanced by co-
administration with fat, thus should be taken immediately
after food.

19. Artesunate + Mefloquine
• Target dose: 4 mg/kg/day Artesunate+
8.3 mg/kg/day Mefloquine
• Once a day for 3 days
• Mefloquine is associated with severe nausea & vomiting,
dizziness, dysphoria, sleep disturbance
• Treatment failure frequently occurs in patients taking
Rifampicin

20. Artesunate + Sulfadoxime-Pyrimethamine
• Target dose: 4 mg/kg/day Artesunate (od x3days) +
at least 25/1.25 mg/kg Sulfadoxime-Pyimethamine
single dose on day 1
• Disadvantage of this combination is that it is not available
as fixed dose combination, reducing the compliance &
adherence of patient to the drugs
• Resistance is increasing due to widespread use of S-P.
• Bettertoavoidinpregnantpatient,FAsupplement

21. 3. Treatment of severe falciparum malaria
Preferred regime Alternative regime
IV Artesunate (60mg): 2.4mg/kg on
admission, followed by 2.4mg/kg at 12h &
24h, then once daily for 7 days.
Once the patient can tolerate oral therapy,
treatment should be switched to a complete
dosage of artemether/lumefantrine for 3
day.
IV Quinine loading 7mg salt /kg over 1hr
followed by infusion IV Quinine 20mg/kg over
4 hrs, then 10mg/kg Q8H.
Plus
Adult & child >8yrs old: Doxycycline
(3.5mg/kg once daily)
or
Pregnant women & child < 8yrs old:
Clindamycin (10mg/kg twice daily). Both drug
can be given for 7 days.
Reconstitute with 5% Sodium Bicarbonate &
shake 2-3min until clear solution obtained.
Then add 5ml of D5% or 0.9%NaCl to create
total volume of 6ml.
Slow IV injection with rate of 3-4ml/min or
IM injection to the anterior thigh.
The solution should be prepared freshly for
each administration & should not be stored.
Dilute injection quinine in 250ml od D5%
and infused over 4hrs.
Infusion rate should not exceed 5 mg salt/kg
per hour.

22. 4. Treatment of malaria caused by p.knowlesi & mixed
infection (p. falciparum + p. vivax)
• Treat as p. falciparum

23. Treatment in specific population & situations
Specific
populations
Preferred regime Alternative regime
Pregnancy Quinine plus clindamycin to be given for
7 day
Artesunate plus Clindamycin
for 7 days is indicated if first
line treatment fails
Lactating
women
Should receive standard antimalarial treatment (including ACTs) except for
dapsone, primaquine and tetracyclines, which should be withheld during
lactation
Hepatic
impairment
Chloroquine: 30-50% is modified by liver, appropriate dosage adjustment
is needed, monitor closely.
Quinine : Mild to moderate hepatic impairment-no dosage adjustment,
monitor closely.
Artemisinins : No dosage adjustment
Renal
Impairment
Chloroquine : ClCr<10ml/min-50% of normal dose.
Hemodialysis, peritoneal dialysis: 50% of normal dose.
Continuous Renal Replacement Therapy(CRRT) :100% of normal dose.
Quinine : .ClCr 10-50ml/min : Administer Q8-12H, CLCr<10ml/min :
administer Q24H,Severe chronic renal failure not on dialysis : initial dose:
600mg followed by 300mg Q12H, Hemo- or peritoneal dialysis: administer
Q24H ,Continuous arteriovenous or hemodialysis: Administer Q8-12H.
Artemisinin : no dosage adjustment.

24. Treatment failure of
uncomplicated malaria
• A failure to clear malarial parasitaemia and/or resolve clinical
symptoms despite the administration of an antimalarial. So
while drug resistance may lead to treatment failure, not all
treatment failures are caused by drug resistance.
• Treatment failure can also be the result of incorrect dosing,
problems of treatment adherence (compliance), poor drug
quality, interactions with other drugs, compromised drug
absorption, or misdiagnosis of the patient. Apart from
leading to inappropriate case management, all these factors
may also accelerate the spread of true drug resistance by
exposure of the parasites to inadequate drug levels.

25. Treatment failure for
uncomplicated malaria
• Treatment failures within 14 days of initial treatment should
be treated with a second-line antimalaria.
• The following second-line treatments are
recommended,
• In order of preference:
- an alternative ACT known to be effective in the region,
o Artesunate plus tetracycline or doxycyclineor
clindamycin (given for a total of 7 days),
o Quinine plus tetracycline or doxycyclineor
clindamycin (given for a total of 7 days).

26. Monitoring & follow-up
• Blood smear should be repeated daily (twice daily in
severe infection). Within 48- 72 hr after start of
treatment, patients usually become afebrile and
improve clinically except in complicated cases.
• All patients should be investigated with
repeated blood film of malarial parasite one
month upon recovery of malarial infection, to
ensure no recrudescence.

27. PREGNANCY & MALARIA
• 10 times high risk to develop malaria & high
tendency to develops complications
• First TM – Quinine / Mefloquine + Clindamycin
for 7 days
• Second & Third TM - Quinine / Mefloquine +
Clindamycin for 7 days
• - Artemether + lumefentrine can be used
• Primaquine & tetracycline never to use
• Frequent investigations & monitioring required

28. • Severe & complicated malaria is an medical
emergency.
• Patient should be referred to tertiary care &
treatment should start urgently
• Patient needs multiple investigations, fluid &
electrolytes correction

30. THANK YOU
9099920286/8849904036

31. Relapse
• Only in P.vivax & P.ovale
• Some sporozoites go under
resting phase in liver, instead
of preceding further in the
cycle
• Later forms hypnozoites &
gives rise to various
symptoms
• Enables survival during
cold winters
• If re-activated new focus
of transmission
Recrudescence
• All species
• Due to failure of
elimination either by
immune system or
treatment failure
• No clearance of parasitemia
but reduced to sub-patent
levels for a time
• A period of 8 weeks is needed
to exclude recrudescence of
drug- resistant parasites

32. Artemether +
Lumefantrine
• Total dose of 5-24 mg/kgArtemether+
29-144 mg/kg Lumefantrine
• Recommended dosage regimen – twice a day for 6 days
(total 6 doses)
• 1st two doses should be given 8hrs apartideally.
• Advantage of this ACT is that lumefantrine is not available
as monotherapy and has never been used as alone for
malaria treatment
• Absorption of Lumefantrine is enhanced by co-
administration with fat, thus should be taken immediately
after food.

33. Artesunate +
Amodiaquine
• Target dose: 4 mg/kg/day (2-10) IV Artesunate +
10 mg/kg/day (7.5-15) Amodiaquine
• Once a day for 3 days
• Side effect of severe neutropenia in patients co-infected
with HIV, esp with those on Zidovudine and/or
Cotrimoxazole.

34. Artesunate +
Mefloquine
• Target dose: 4 mg/kg/day (2-10) Artesunate+
8.3 mg/kg/day (5-11) Mefloquine
• Once a day for 3 days
• Mefloquine is associated with severe nausea & vomiting,
dizziness, dysphoria, sleep disturbance
• Treatment failure frequently occurs in patients taking
Rifampicin

35. Artesunate + Sulfadoxime-Pyrimethamine
• Target dose: 4 mg/kg/day (2-10) Artesunate (od x3days)+
at least 25/1.25 mg/kg Sulfadoxime-Pyimethamine
single dose on day 1
• Disadvantage of this combination is that it is not available
as fixed dose combination, reducing the compliance &
adherence of patient to the drugs
• Resistance is increasing due to widespread use of S-P.

36. Dihydroartemisinin-
Piperaquine
• Target dose: 4 mg/kg/day (2-10) Dihydroartemisinin +
18 mg/kg/day (16-27) Piperaquine
• Once a day for 3 days
• High fat meals should be avoided as it increases the
absorption of Piperaquine, thereby increasing the risk
of potentially arrhythmogenic delayed ventricular
repolarization (ECG – prolonged QT interval)
• Treatment failure is very common in young children
& pregnant women