This document summarizes information about malaria, including that it affects 3.3 billion people globally and causes 900,000 deaths annually. It outlines high risk groups like children under 5 and pregnant women. Four Plasmodium species cause malaria in humans. Diagnosis is usually by microscopy or rapid diagnostic tests detecting parasites. Treatment involves artemisinin-based combination therapies over 3 days for uncomplicated cases. Severe malaria requires parenteral artesunate or quinine for a minimum of 24 hours before completing treatment. Prevention involves insecticide-treated bed nets and intermittent preventive treatment for vulnerable groups.

1. Aduragbenro Adedapo

2. Malaria
 Globally 3.3 billion people are at risk of malaria
 0.25 billion affected, 900 000 deaths annually (WHO,
2009)
 80-90% of the deaths occur in Africa (WHO, 2012)
High Risk Groups
 Children under 5 years
 Pregnant women (Maternal anaemia, still birth, LBW)
 HIV/AIDs
 Non-immune travellers

3. Aetiological Agent of malaria in man
 Plasmodium falciparum, P. malariae, P. ovale and P.
vivax cause malaria in humans.
 P. Knowlesi, monkey malaria parasite, have been
reported to cause human malaria in parts of SouthEast Asia. Potential cause of malaria for travellers

4. Malaria Parasite Genome
 Complete genome sequence has been determined for:
 P.falciparum, P.vivax and P.knowlesi

5. Malaria – mode of transmission
 Bite of female Anopheles mosquito
Others:
 Congenital (mother to child)
 Blood transfusion
 Contaminated needle prick

6. Life cycle of malaria parasite
In mosquitoes
 Sexual ------- sporozites
In humans
 Liver stages (Primary, hypnozoites – P.vivax & P.ovale)
 Red blood cells – asexual and gametes

7. Life cycle of malaria parasite (wikiped)

8. Clinical Features of Malaria
 Fever
 Malaise
 Headache
 Myalgia
 Anorexia
 Vomiting
 Bitter taste in the mouth
Other symptoms: vague abdominal pain, epigastric pain,
pruritus, dry cough, lethargy

9. Malaria diagnosis
Clinical:
“least expensive”
imprecise but the basis of treatment when laboratory
support is out of reach

10. Parasite-based diagnostic methods
Microscopy of Giemsa stained blood smears
Alternatives: detection of malaria antibodies by –
indirect immunofluorescence assay (IFA);
enzyme-linked immunosorbent assays (ELISA)
Detection of malaria antigens
Immunochromatographic assay: basis of rapid
diagnostic tests (RDTs) – Parasight-F test, OptiMAL IT
Fluorescent stain – Quantitative Buffy Coat (QBC)
Molecular methods: DNA probes and polymerase chain
reaction

11. Malaria diagnosis
 Microscopy is the gold standard: for prompt
parasitological confirmation
 alternatively by rapid diagnostic tests (RDTs)
 Treatment solely on the basis of clinical suspicion
should only be considered when a parasitological
diagnosis is not accessible.

12. Recommended Interventions
 Vector Control- Insecticide Treated Mosquito nets,
Indoor Residual Spraying, +/- larval control
 Chemoprevention – for vulnerable group viz pregnant
women & infants (IPTp, IPTi) ; non-immune
 Confirmation of malaria diagnosis – microscopy or
rapid diagnostic tests
 Timely treatment – use appropriate antimalarial drug

13. Management options
 Prevention
 Prophylaxis
 Therapy: Uncomplicated malaria, severe malaria,
malaria in special conditions
 Orthodox medicine; traditional drugs – (Neem or
dongoyaro etc)
 Home management of malaria (HMM)
 Vaccines???

14. Treatment of malaria
 Artemisinin based combination therapy (ACTs): first-
line treatment for P. falciparum malaria.
 P. vivax malaria : chloroquine where it is effective, or
an appropriate ACT in areas where P. vivax is resistant
to chloroquine.
 Treatment of P. vivax should be combined with a 14day course of primaquine to prevent relapse.

15. 2006 Recommendations for
uncomplicated P. falciparum
malaria.
Artemisinin-based combination therapies (ACTs)
Examples are:
 artemether plus lumefantrine,
 artesunate plus amodiaquine,
 artesunate plus mefloquine, and
 artesunate plus sulfadoxine-pyrimethamine.
Addition WHO 2010 guideline
 Dihydroartemisinin plus piperaquine (DHA+PPQ)

16. Second-line antimalarial treatment
 alternative ACT known to be effective in the
region;
 artesunate plus tetracycline or doxycycline or
clindamycin; any of these combinations to be
given for 7 days;
 quinine plus tetracycline or doxycycline or
clindamycin; any of these combinations should be
given for 7 days

17. Currently recommended ACTS
for treatment of uncomplicated falciparum malaria in
alphabetical order are:
 artemether plus lumefantrine,
 artesunate plus amodiaquine,
 artesunate plus mefloquine,
 artesunate plus sulfadoxine-pyrimethamine,
 dihydroartemisinin plus piperaquine.

18. artemether plus lumefantrine
 6-dose regimen over a 3-day period.
 (5–14 kg: 1 tablet; 15–24 kg: 2 tablets; 25–34 kg: 3
tablets; and > 34 kg: 4 tablets), given twice a day for 3
days.
 This extrapolates to 1.7/12 mg/kg body weight of
artemether and lumefantrine, respectively, per dose,
given twice a day for 3 days
 Available as a fixed-dose formulation tablets
containing 20 mg of artemether and 120 mg of
lumefantrine.

19. artesunate plus amodiaquine
 4 mg/kg/day artesunate and
 10 mg/kg/day amodiaquine once a day for 3 days
 Available as 50 mg of artesunate and 153 mg base of
amodiaquine separately &
 As fixed dose formulations containing 25/67.5 mg,
50/135 mg or 100/270 mg of artesunate and
amodiaquine

20. artesunate plus mefloquine
 4 mg/kg/day artesunate given once a day for 3 days
 and 25 mg/kg of mefloquine either split over 2 days as
15mg/kg and 10mg/kg or
 over 3 days as 8.3 mg/kg/day once a day for 3 days
 Available as 50 mg of artesunate and 250 mg base of
mefloquine

21. artesunate plus sulfadoxinepyrimethamine
 4 mg/kg/day artesunate given once a day for 3 days
 and a single administration of 25/1.25 mg/kg
sulfadoxine-pyrimethamine on day 1
 Available as 50 mg of artesunate tablet; and tablets
containing 500 mg of sulfadoxine and 25 mg of
pyrimethamine

22. dihydroartemisinin plus
piperaquine
 4 mg/kg/day dihydroartemisinin and
 18 mg/kg/day piperaquine once a day for 3 days
 Available as 40 mg of dihydroartemisinin and 320 mg
of piperaquine

23. Special conditions: Pregnancy
First trimester: Quinine is safe in 1st trimester
 quinine plus clindamycin to be given for 7 days
(artesunate plus clindamycin for 7 days is indicated if
this treatment fails);
 an ACT is indicated only if this is the only treatment
immediately available, or if treatment with 7-day quinine
plus clindamycin fails or uncertainty of compliance with a
7-day treatment.
Second and third trimesters:
 ACTs known to be effective in the country/region or
artesunate plus clindamycin to be given for 7 days, or
quinine plus clindamycin to be given for 7 days.

24. Pregnancy - first trimester
 Quinine plus clindamycin for 7 days (and quinine
monotherapy if clindamycin is not available).
 Artesunate plus clindamycin for seven (7) days is
indicated if this treatment fails

25. Caution in Pregnancy!
 Quinine is associated with an increased risk of
hypoglycaemia in late pregnancy, and it should be
used only if effective alternatives are not available.
 Primaquine and tetracyclines should not be used in
pregnancy

26. Lactating women & children
Lactating women:
 Standard antimalarial treatment (including ACTs)
except for dapsone, primaquine and tetracyclines.
Infants and young children:
 ACTs for first-line treatment with attention to accurate
dosing and ensuring the administered dose is retained.

27. Caution in lactation and children!!
 Tetracycline is contraindicated in breastfeeding
mothers because of its potential effect on the infant’s
bones and teeth.
 Primaquine should not be used in nursing women,
unless the breastfed infant is not G6PD-deficient

28. Non-immune individuals
Travellers returning to non-endemic countries:
 atovaquone-proguanil;
 artemether-lumefantrine;
 quinine plus doxycycline or clindamycin.

29. Non-immune individuals
 atovaquone plus proguanil (15/6 mg/kg [adult dose – 4
tablets] once a day for 3 days)
 Quinine, doxycycline (3.5 mg/kg once a day) or
clindamycin (10 mg/kg twice a day)

30. Non-immune individuals
 Chemoprophylaxis already?
 The same medicine should not be used for treatment

31. Prevention of malaria in nonimmune
 Atovaquone/proguanil (Malarone) 250/100mg daily
 Chloroquine (if parasite sensitive) 300mg base weekly
 Doxycycline
 Hydroxychloroquine
 Mefloquine
 Primaquine
100mg daily
310mg base weekly
228mg base weekly
30mg daily

32. Malaria and HIV
 Prompt treatment
 Treatment or intermittent preventive treatment
with sulfadoxine-pyrimethamine should not be
given to HIV-infected patients receiving
cotrimoxazole (trimethoprim plus
sulfamethoxazole) prophylaxis.
 Avoid amodiaquine-containing ACT regimens
treatment in HIV-infected patients on zidovudine
or efavirenz should, if possible,

33. Severe Malaria
 Demonstration of P. falciparum asexual parasitaemia
in a patient +
 no other obvious cause of symptoms +
 the presence of one or more of the following clinical or
laboratory features

34. Clinical Features of Severe Malaria
 impaired consciousness or unrousable coma
 prostration, i.e. generalized weakness so that the patient is
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unable walk or sit up without assistance
failure to feed
multiple convulsions – more than two episodes in 24 h
deep breathing, respiratory distress (acidotic breathing)
circulatory collapse or shock, systolic blood pressure < 70
mm Hg in adults and < 50 mm Hg in children
clinical jaundice plus evidence of other vital organ
dysfunction
Haemoglobinuria, abnormal spontaneous bleeding

35. Laboratory Parameters for Severe
Malaria
 Hypoglycaemia (blood glucose < 2.2 mmol/l or < 40 mg/dl)
 Metabolic acidosis (plasma bicarbonate < 15 mmol/l)
 Severe normocytic anaemia (Hb < 5 g/dl, packed cell
volume < 15%)
 Haemoglobinuria
 Hyperparasitaemia
(> 2%/100 000/μl in low intensity transmission areas or
> 5% or 250 000/μl in areas of high stable malaria)
 Hyperlactataemia (lactate > 5 mmol/l)
 Renal impairment (serum creatinine > 265 μmol/l)

36. Severe Malaria – treatment
options
 the cinchona alkaloids (quinine and quinidine) and
the
 artemisinin derivatives (artesunate, artemether and
artemotil or beta arteether)

37. Severe Malaria
For adults, artesunate IV or IM:
 quinine is an acceptable alternative if parenteral
artesunate is not available.
For children :
 artesunate IV or IM;
 quinine (IV infusion or divided IM injection);
 artemether IM (should only be used if none of the
alternatives are available as its absorption may be
erratic).

38. Non-immune/Travellers: severe
malaria
 In the management of severe malaria outside endemic
areas
 There may be unavailability or delay in obtaining
artesunate, artemether or quinine
 parenteral quinidine if available should be given with
careful clinical and electrocardiographic monitoring.

39. Severe Malaria - not recommended
 Parenteral chloroquine because of widespread
resistance &
 Intramuscular sulfadoxine-pyrimethamine

40. Quinine
 loading dose of quinine (i.e. 20 mg salt/kg body weight
– twice the maintenance dose) reduces the time
needed to reach therapeutic plasma concentrations.
 The maintenance dose of quinine (10 mg salt/kg body
weight) is administered at 8-h intervals, starting 8 h
after the first dose
 administered as a slow, rate-controlled infusion
(usually diluted in 5% dextrose and infused over 4 h

41. Quinidine
 Is more toxic than quinine, it causes hypotension and
QT prolongation
 Only to be used if no other effective parenteral drugs
are available.
 Its use requires electrocardiographic monitoring and
frequent assessment of vital signs

42. Severe malaria (Rx - ctd)
 Give parenteral antimalarials in the treatment of
severe malaria for a minimum of 24 h, once started
(irrespective of the patient’s ability to tolerate oral
medication earlier) and, thereafter, complete
treatment by giving a complete course of ACTs

43. Severe malaria – after parenteral
drug(s) complete treatment by
giving:
 artemether plus lumefantrine,
 artesunate plus amodiaquine,
 dihydroartemisinin plus piperaquine,
 artesunate plus sulfadoxine-pyrimethamine,
 artesunate plus clindamycin or doxycycline,
 quinine plus clindamycin or doxycycline.

44. Severe Malaria: pre-referral
treatment options
 rectal artesunate, quinine IM, artesunate IM,
artemether IM
 and promptly refer to an appropriate facility for further
treatment.

45. Poser!!!
 Intravenous (IV) artesunate should be used in
preference to quinine for the treatment of severe P.
falciparum malaria in adults.
 “T3: Test. Treat. Track.” initiative, urging endemic
countries and stakeholders to scale up diagnostic
testing, treatment, and surveillance for malaria

46. Management of Antimalarial drug
Resistance
 Therapeutic drug efficacy studies: to detect suspected
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artemisinin resistance
artemisinin resistance: increase in parasite clearance time,
as evidenced by ≥ 10% of cases with parasites detected on
day 3 after treatment with an ACT
Additional studies: (i) In vitro studies to measure the
intrinsic sensitivity of parasites to antimalarial drugs
(ii) Molecular marker studies to identify genetic mutations
and subsequently confirm the presence of mutations in
blood parasites
(iii) pharmacokinetic studies to character drug absorption
& drug action in the body

47. References
 Vinetz JM, Clain J, Bounkeua V, Eastman RT, Fidock D. Chemotherapy
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of malaria. In: Goodman and Gilman’s Pharmacological Basis of
Therapeutics, 12TH Edition, Laurence Brunton, Bruce Chabner and
Bjorn Knollman (Editors). United States: McGraw-Hill, 2011 pp 13841418.
World Health Organization. World Malaria Report, 2012. Available at:
http://www.who.int/malaria/publications/world_malaria
report_2012/wmr/2012_full_report.pdf
WHO 2010 Guidelines for the treatment of malaria 2nd Edition
National Guidelines for the diagnosis and treatment of malaria 2011
Wongrichanalai C, Barcus MJ, Muth S, Sutamihardja A, Wernsdorfer
WH. A review of malaria diagnostic tools: microscopy and rapid
diagnostic test (RDT).. Am J Trop Med 2007; 77(6suppl) 119-27

48. THANK YOU
 Thank You For Your Attention
 All the best in all your endeavours – practice and
examinations.