A presentation on MALARIA in the Tropics

1. MALARIA
By
Dr Ibrahim Taoheed Abiodun
State Specialist Hospital Akure

2. OUTLINES
• INTRODUCTION
• EPIDEMIOLOGY
• PATTERN OF MALARIA EDEMICITY
• MALARIA IN NIGERIA
• ETIOLOGY
• PATHOPHYSIOLOGY
• SIGNS AD SYMPTOMS
• MANAGEMENT
• COMPLICATIONS
• CONCLUSION

3. INTRODUCTION
• Malaria has infected humans for over 50,000 years and may have
been a human pathogen for the entire history of our species. Close
relatives of the human malaria parasites remain common in
chimpanzees. References to the unique periodic fevers of malaria are
found throughout recorded history, beginning in 2700 BC in China.
The term malaria originates from medieval Italian: mala aria — “bad
air”; and the disease was formerly called ague or marsh fever due to
its association with swamps and marsh land.

4. • Malaria is the most important, widespread and most dangerous of all the
parasitic disease. It is one of the most common infectious diseases and an
enormous public health problem of global concern. The disease is a major
cause of morbidity and mortality in Nigeria where it is endemic.
• In Africa today, malaria is understood to be both a disease of poverty and a
cause of poverty. Annual economic growth in countries with high malaria
transmission has historically been lower than in countries without malaria.
Economists believe that malaria is responsible for a growth penalty of up to
1.3% per year in some African countries. When compounded over the
years, this penalty leads to substantial differences in GDP between
countries with and without malaria and severely restrains the economic
growth of the entire region.

5. • Malaria also has a direct impact on Africa's human
resources. Not only does malaria result in lost life and
lost productivity due to illness and premature death,
but malaria also hampers children's schooling and social
development through both absenteeism and permanent
neurological and other damage associated with severe
episodes of the disease.

6. EPIDEMIOLOGY
• Malaria occurs in the sub-tropical and
tropical areas of the world. People from
areas where malaria is endemic develop
partial immunity, hence older children and
adults in such areas but they may also still
have severe malaria.
• Some factors responsible for variations in
malaria endemicity are:
High temperature >25oC
Low altitude < 2,000m above sea level
High humidity >60%
Heavy rainfall >125cm

7. • Most important parasitic disease of man
• Up to 500 million people worldwide suffer from it annually
• 90% of malaria associated morbidity and mortality occurs in Sub-
Saharan Africa
• One new case every 10 seconds
• Results in 3 – 5 million deaths each year
• Every 30 seconds, an African child dies from malaria
• Affects 5x as many people as AIDS, leprosy, measles, TB and RTA
combined.

8. PATTERN OF MALARIA EDEMICITY
• Stable Malaria- Malaria is transmitted all year round, but may have
seasonal variation. Adults living here may acquire some immunity and
are hence unlikely to develop severe malaria
• Unstable Malaria- It is characterized by intermittent transmission that
may be bi-annual or variable. Epidemics occur due to poor immunity
against malaria
• Malaria free-areas- No immunity whatsoever, hence all are prone to
severe malaria

9. STABLE MALARIA
• In areas of stable malaria like Nigeria;
• Infants and young children are more susceptible to malaria than older
children and adults.
• They are thus the main victims of infestation and probably represent the
main reservoir as well.
• Childhood is associated with considerable morbidity and mortality.
• If the child survives however, he/she achieves a state of “premunition’ i.e a
form of immunity whereby malaria infestation causes little or no problems
• Older children have milder symptoms
• Adults rarely develop severe malaria. Pregnancy, however poses a special
threat.

10. Malaria in Nigeria
•Intense transmission all year round, but higher during rainy
season (increased breeding sites)
•Commonest cause of hospital attendance in all age
groups accounting for 63% of outpatient visits
•Children U5 have 2 – 4 attacks per year
•Responsible for 30% of childhood mortality and 25% infant
mortality
•> 300,000 children below the age of five years die every
year from malaria

11. Economic Implications of Malaria in Nigeria
• Malaria is a cause and consequence of poverty – the poorest are the
most vulnerable
N132 billion is lost to malaria annually:
Prevention
Treatment costs
Transport to source of treatment,,
Absenteeism leading to loss of man hours, reduction in labour supply &
productivity

12. A. Hypoendemicity - little transmission and the disease has little effect
on the population.Spleen rate <10%.
B. Mesoendemicity - varying intensity of transmission; typically
found in the small, rural communities of the sub-tropics.S.R 11-
50%.
C. Hyperendemicity - intense but seasonal transmission; immunity is
insufficient to prevent the effects of malaria on all age
groups.S.R51-75%.

13. D. Holoendemicity - intense transmission occurs throughout the year. As
people are continuously exposed to malaria parasites, they gradually
develop immunity to the disease. In these areas, severe malaria is
mainly a disease of children from the first few months of life to age 5
years. Pregnant women are also highly susceptible because the natural
immune defence mechanisms are impaired during
pregnancy.S.R>75%.

14. ETIOLOGY
• A protozoan infection caused by invasion of human red blood cells by
any of the four species of the plasmodium parasite
• Plasmodium falcipoarum
• Plasmodium vivax
• Plasmodium ovale
• Plasmodium malaria
• Plasmodium knowlesi

15. MODE OF TRANSMISSION
• Naturally acquired from the bite of a female anopheles mosquito
infected with a specie of the plasmodium parasite
• Africa has the most efficient vector species in the world – Anopheles
gambiae
• Can also be acquired through blood transfusion, needle sharing,
organ transplantation or from mother to foetus resulting in congenital
malaria

16. M.O.T conti………………
• The source of malaria infection is either a sick or symptomless carrier
of the parasite
• Natural transmission depends on the presence of and relationship
between the three epidemiological factors.
• Reservoir- man (for human plasmodia)
• Agent of Infection- gametocytes of plasmodium
• Vector of transmission- Anopheles mosquito

17. INCUBATION PERIOD
• Plasmodium falciparum; 9-15days
• Plasmodium vivax;12-18days
• Plasmodium ovale;12-18days
• Plasmodium malaria;18-37days
• Plasmodium knowlesi
• Plasmodium falciparum accounts for 80-90% of malaria infection
alone or In combination with one or more other species.

18. Life cycle of the malaria parasite
• The life cycle and transmission pattern of all four species are
fundamentally similar, though there are differences that are
important in relation to pathogenicity and treatment.
• It occurs in 2 phases,
• a sexual phase in the mosquito
• an asexual phase in man

19. In the mosquito
• This sexual phase is called sporogony
• Male and female gametocytes obtained from the ingestion of human
blood fuse within the gut of the mosquito to form zygotes.
• The zygote now develops into OOKINETTE which penetrates the gut
wall of the mosquito where it becomes the young OOCYST –
segmented OOCYST.
• Which penetrates the salivary glad of the mosquito forming
SPOROZOITES.

21. In Man
• This asexual phase is called schizogony;
• The pre-erythrocytic stage (6 -15 days) :
• Sporozoites in the salivary glands of the female anopheles mosquito
are injected into the blood stream during a bite.
• Within 30-45 minutes, they reach the liver sinusoids and enter the
cytoplasm of the hepatic cells.
• Growth and nuclear division occur rapidly and they develop into liver
schizonts, which contain many merozoites.
• When the liver schizonts are ripe, they rupture to release thousands
of merozoites into the blood stream.

22. The pre-erythrocytic stage (6 -15 days)
• In P.vivax and P.ovale infections, some sporozoites do not develop;
• Remain inert as sleeping forms or hypnozoites
• Become active months to years later
• Cause relapses which characterize infection with these two species.

23. The erythrocytic stage
• The merozoites rapidly invade red blood cells
• Within they develop into trophozoites (ring forms), which grow by
feeding on haemoglobin in the cells.
• The fully developed trophozoites now divide asexually several times,
to form erythrocyte schizonts, which contain 8 – 32 merozoites each,
depending on the species.
• With time, the red blood cells become depleted in haemoglobin,
rigid, spherical and eventually rupture to release merozoites, malaria
pigment and toxins into the plasma - merogony.

24. Periodicity of fever
• Oce merozoites are release they trigger inflammatory
resposes which elaborate some cytokines;I 1,6,8,ad tnf
alpha.
• Fever every 48hrs (tertian)-P.ovale and P.vivax
• Fever every 72hrs(quartan)-P.malaria
• Malignant tertian fever In P.falciparum ad its asychronous.

25. The erythrocytic stage
• At merogony, the merozoites rapidly invade other erythrocytes to
begin new cycle of schizogony with more cells being destroyed.
• Each erythrocytic schizogony cycle lasts 48 hours for P.falciparum,
vivax and ovale and 72 hours for P.malariae.
• After a series of cycles, some of the merozoites entering the red cells
develop into sexual forms – male and female gametocytes, which
must be ingested by a female anopheles mosquito for the life-cycle to
continue.

26. The erythrocytic stage
• For P.falciparum, not all stages of development occur in peripheral
blood.
• At approx 24 – 26 hours of parasite development, infected rbcs
develop knob-like projections on their membranes, which enable
them to adhere to vascular endothelium – a process called cyto –
adherence
• This occurs on the walls of venules and capillaries in vital organs and
results in the disappearance of the parasitized red cells from
circulation. This process is called sequestration.
• Thus unlike other species, falciparum trophozoites complete their
development into schizonts in the microvasculature of deep tissues,
not in circulating blood

27. Patho-physiology of Malaria
• The patho - physiological changes in malaria result from;
• erythrocyte destruction
• liberation of parasite and erythrocyte material into the circulation
• sequestration of P.falciparum infected erythrocytes in the
microcirculation of vital organs
• the host’s reaction to these events

28. Release of Cytokines
• Cytokines - host substances secreted by sensitized T cells in response to
subsequent exposure to an antigen.
• At merogony, glycolipid material with properties of bacterial endotoxin is
released.
• Induces the activation of the cytokine cascade
• First, tumor necrosis factor (TNF) and interleukin-1 (IL-1) are produced then
others such as IL-6 and IL-8
• These cytokines are responsible for many of the C.Fs of malaria infestation,
especially the fever and malaise.
• → suppression of erythropoesis → anaemia
• →inhibition of gluconeogenesis → hypoglycaemia
• →promote cytoadherence →sequestration →ischaemia →pains
• → Also important mediators of parasite destruction by activating leucocytes and
other cells to release free radicals, nitric oxide, and lipid peroxides

29. Sequestration
• Occurs in deep capillaries and venules of vital organs such as the
brain, lungs, kidneys etc.
• Causes obstruction in the microcirculation of affected organs, with
resultant tissue ischaemia.
• Leads to reduction in oxygen and substrate supply with consequent
alteration of the metabolism in the host tissues.
• Shift from aerobic glycolysis to anaerobic glycolysis with consequent
lactic acidosis
• Acute tubular necrosis with resultant renal failure in severe malaria is
also a consequence

30. Anemia
• Multi-factorial
• Obligatory destruction of red cells (haemolysis) containing parasites
occurs at merogony.
• Autoimmune destruction of parasitized and non-parasitized cells
• Consumption of haemoglobin by parasites
• Increased splenic removal of spherical, rigid, non-deformable
erythrocytes from the circulation
• TNF mediated impaired erythropoesis
• All these factors thus act together resulting in shortening of red cell
survival.

31. CNS abnormalities
• Cerebral malaria – presence of impaired consciousness in a case of
confirmed P.falciparum malaria, in which other encephalopathies have
been excluded
• Raised intra-cranial pressure probably due to increase in cerebral volume
not oedema.
• Increased volume is from circulating blood required to maintain cerebral
perfusion, and the sequestered biomass of intra cerebral parasites
• Coma is thought to be due to the interference with neurotransmission.
• The cytokines that are released in response to the sequestered parasites in
the brain tissue increase the production of nitric oxide, a potent inhibitor
of neurotransmission, by leucocytes, smooth muscle cells, microglia and
vascular endothelium.
• Probably, this local synthesis of nitric oxide may be relevant to the
impairment of consciousness.

32. CNS abnormalities
• Convulsions
• May be due to
• Direct effects of parasites on the brain
• Hyperpyrexia – temp ≥ 40 deg
• Hypoglycaemia – blood sugar < 40mg/dl
• Hypoxaemia from severe anaemia – PCV < 20%
• Effects of herbal concoctions
• Severe acidosis – serum HCO3 < 15meq/l
• Severe hyponatraemia – serum Na < 120 meq/l

33. Hypoglycemia
• Impaired gluconeogenesis in the liver
• Decreased intake (prolonged fasting)
• Increased glucose utilization - maturing parasites consume large
quantities of glucose from the plasma
• Glycogen depletion
• In the course of treatment with quinine which stimulates the
pancreas to secrete insulin leading to hypoglycemia

34. Respiratory Distress
• Causes; anaemia, acidosis, aspiration
• Pulmonary oedema – due to excessive fluid replacement by IV
infusion, especially if there is renal failure.
• Respiratory Distress Syndrome could also be due to the direct effect
of parasites sequestered in the lungs possibly through release of
cytokines.

35. Renal failure
• In malaria, renal failure is as a result of acute tubular necrosis, hence
fully reversible if patient can be kept alive.
• Can also result from low blood pressure from dehydration or shock.

36. Acidosis
• Relative shortage of oxygen in tissues occupied by sequestered
parasites.
• This lack of oxygen forces tissues to get their energy by other
biochemical pathways not dependent on oxygen → anaerobic
glycolysis → release of lactic acid → metabolic acidosis.

37. Haemoglobinuria
Results from massive intravascular haemolysis (rapid breakdown of red
blood cells in circulation)
Could also be caused by use of oxidant anti-malarials in children with
G6PD deficiency (e.g drugs like sulphonamides and primaquine)

38. Clinical features of Malaria
Range from asymptomatic to mild to severe dz
Uncomplicated malaria- No life threatening
manifestations
Severe malaria – Asexual P.falciparum
parasitaemia with life threatening clinical or
laboratory features and no other confirmed
cause

39. Clinical features of Uncomplicated Malaria
Symptom Signs
pyrexia (temperature>37.5C)
fever*
headache enlarged spleen & liver
chills (feeling cold)
rigors (shivering) pallor
general weakness
body pains
abdominal pain,
nausea with or without vomiting
loss of appetite
n.b

40. WHO criteria for Severe Malaria
Asexual P. falciparum parasitaemia with one or more of the following clinical and
laboratory features and no other confirmed cause for their symptoms;
CLINICAL LABORATORY
Prostration Severe anaemia
Persistent (intractable) vomiting Hypoglycaemia
Impaired consciousness Acidosis
Respiratory distress Hyperparasitaemia
Multiple convulsions
Circulatory collapse
Pulmonary oedema
Abnormal bleeding
Jaundice
Haemoglobinuria
Oliguria (Renal failure)

41. Clinical Diagnosis
• Detailed history-taking and physical examination essential
• Age, place of residence, travel hx, ask about symptoms of malaria &
other diseases; cough, diarrhoea, ear pain and skin rashes, within the
last three months, urinary frequency
• Signs
• Increased body temperature >37.5C
• Pallor
• Enlarged spleen ± liver
• Exclude signs of severe disease

42. LABORATORY DIAGNOSIS
Laboratory investigation is aimed at confirming diagnosis, assess
severity of disease and exclude other possible causes of severe
disease.
. Before, the “+” system was used to make diagnosis, which was not
appropriate for monitoring severe disease because it will not
objectively show changes in the parasite load.
• . Presently, there are newer methods and they can be classified into 2:
a. Microscopic and
b. Non-microscopic tests.

43. A.MICROSCOPIC TESTS:
The most economic, preferred, and reliable diagnosis of malaria is
microscopic examination of blood films because each of the four
major parasite species has distinguishing characteristics.
These involve staining and direct visualization of the parasite under
the microscope.
• Peripheral smear
• Quantitative Buffy Coat (QBC) test

44. Peripheral smear study:
• Two sorts of blood film are traditionally used. Thin films are similar to
usual blood films and allow species identification because the
parasite's appearance is best preserved in this preparation. Thick
films allow the microscopist to screen a larger volume of blood and
are about eleven times more sensitive than the thin film, so picking
up low levels of infection is easier on the thick film, but the
appearance of the parasite is much more distorted and therefore
distinguishing between the different species can be much more
difficult. With the pros and cons of both thick and thin smears taken
into consideration, it is imperative to utilize both smears while
attempting to make a definitive diagnosis.

45. P.B.S……..
• Giemsa stained-thick blood films are the basis for microscopic
diagnosis with a standard of looking at 100 fields at a magnification of
600-700 (equivalent to 0.25 µL of blood) and limit of detection usually
being 10-20 parasites per µL of blood. Thus, a negative slide does not
indicate absence of malaria in the patient. Repeat blood film should
be done after a few hours.
• Criteria suggestive of P. falciparum infection
• Prominent non-pigmented ring forms
• Double chromatin
• Diagnostic crescent shaped gametocytes
• The infected red cells are not enlarged and are without the pink stippling (Schuffner
dots).

46. The old semi-quantitative method used is described thus:
• + = 1-10 parasites/100 thick film fields
• ++ = 11-100 parasites/100 thick film fields
• +++ = 1-10 parasites/1 thick film field
• ++++ = >10 parasites/1 thick film field
. The newer method used involves counting infected red cells in
relation to a pre- determined number of white blood cells (WBCs) and
an average of 8000/µL is taken as the standard. 200 WBCs are
counted in 100 fields (0.25µL of blood).
. All parasite forms – sexual and asexual; and species are counted
together.

47. If >10 parasites are counted, this formula can be used to get the number of
parasites/µL :
(No. of parasites counted/ No. of WBCs counted) x 8000
If <9 parasites are counted, 500 WBCs should be counted and the formula
would be:
No. of parasites counted x 16

48. Quantitative Buffy Coat (QBC) test:
• Quantitative Buffy Coat (QBC) test:
The test is used for the identification of malaria parasite in the
peripheral blood.
It is fast, easy and said to be more sensitive than the
traditional thick film examination.
The process involves staining of the centrifuged and
compressed red cell layer with acridine orange and its
examination under UV light source.

49. B.NON-MICROSCOPIC TESTS:
I. Field tests
In areas where microscopy is not available, or where laboratory staff are not
experienced at malaria diagnosis, there are antigen detection tests that require
only a drop of blood.
 Immunochromatographic tests (also called Malaria Rapid
Diagnostic Tests (RDTs); Antigen-Capture Assay or "Dipsticks") have been
developed, distributed and field-tested. These tests use finger-stick or venous
blood, the completed test takes a total of 15-20 minutes, and a laboratory is not
needed. The threshold of detection by these rapid diagnostic tests is in the
range of 100 parasites/µl of blood compared to 5 by thick film microscopy.
There are 2 types: Paracheck-Pf (Para Sight F) and OptiMAL-IT.

50. The first rapid diagnostic tests were using P. falciparum Glutamate
dehydrogenase antigen (Paracheck-Pf). PGluDH was soon replaced by
P.falciparum lactate dehydrogenase, a 33 kDa oxidoreductase [EC
1.1.1.27] (OptiMAL-IT). It is the last enzyme of the glycolytic pathway,
essential for ATP generation and one of the most abundant enzymes
expressed by P.falciparum.
PLDH does not persist in the blood but clears about the same time as the
parasites following successful treatment. The lack of antigen persistence
after treatment makes the pLDH test useful in predicting treatment failure.
In this respect, pLDH is similar to pGluDH.
The OptiMAL-IT assay can distinguish between P. falciparum and P.
vivax because of antigenic differences between their pLDH isoenzymes.
OptiMAL-IT will reliably detect falciparum down to 0.01% parasitaemia and
non-falciparum down to 0.1%.
Paracheck-Pf will detect parasitaemias down to 0.002% but will not
distinguish between falciparum and non-falciparum malaria.
Thus, OptiMAL-IT is sensitive and specific, while Paracheck-Pf is
more sensitive but not specific.

51. II. ELISA (Enzyme-Linked ImmunoSorbent Assay)
III. IFA (Indirect Fluorescent Antibody test) : it’s more accurate . They detect
malarial antibodies in blood or serum by immunosorbent assay.
IV. Molecular Diagnosis – e.g. Polymerase Chain Reaction (PCR) used to
detect parasite DNA. This technique is more accurate than microscopy.
Using the non-isotopically labelled probe following PCR amplification, it is
possible to detect <5 parasites/10µL blood and is specie specific.
However, it is expensive, and requires a specialized laboratory. Moreover,
levels of parasitaemias are not necessarily correlative with the
progression of disease, particularly when the parasite is able to adhere to
blood vessel walls.

52. Treatment of Malaria
• Aims
• To fight an established infestation/infection;
• Includes;
• Elimination of the parasite
• Supportive measures to overcome the morbidity associated
with the infection
• Monitoring to ensure early diagnosis and treatment of
complications, which can lead to death within hours.

53. • There are nine groups of antimalarial drugs in current use:
• Cinchona alkaloids (quinine, quinidine)
• 4 aminoquinolones (Chloroquine, amodiaquine)
• 8 aminoquinolines (primaquine, pamaquine)
• Biqanides (proguanil,chlorproguanil)
• Diaminopyrimidines (Pyrimethamine)
• Anti – folates; Sulphonamides and sulphones
• Quinoline methanol (mefloquin)
• Antibiotics (tetracycline, erythromycin)
• Quinghaosu (arthemeter)
• Phenanthrene methanol(Halfan)

54. GOAL OF ANTIMALARIAL TREATMENT POLICY
The primary goal of treatment in malaria is to cure the
patient of the infection and thereby reduce morbidity
and mortality.
A second purpose is to encourage rational drug use to
prevent or delay the development of anti-malarial drug
resistance.

55. The New National Antimalarial Treatment
Policy
Released in May 2005 by the Federal
Ministry of Health in response to
overwhelming evidence that
Chloroquine, S-P, Halofantrine etc
were no longer adequate for the
treatment of malaria

56. Rationale for Policy Change
Resistance;
• ability of the plasmodium parasite to survive or even
multiply in the presence of minimum inhibitory
concentrations of drug in the blood stream
• cause of great concern over the past 10 to 20 years
resulting in increased morbidity and mortality
• potent hindrance to the attaining the goal of the RBM
initiative

57. Classification of Drug resistance
Response Symbol Evidence
Sensitive S Asexual parasites disappear
by Day 6. No recrudescence
by Day 14
Resistance R 1 Asexual parasites disappear
by Day 6
Reappear by Day 7
Reappear by Day 14
RII Asexual parasitaemia reduces
by 25% within 48 hrs but no
clearance
R III Asexual parasitaemia reduces
by less than 75% or
continues to rise

58. Status Of Anti-malarial Drug Resistance
TREND OFCHLOROQUINESENSITIVITY IN NIGERIA
0
20
40
60
80
100
120
1980 1981 1984 1988 1989 1990 1991 1995 1997 2002
Year
%Sensitivity

59. Rationale for Policy Change
•In 2001, the WHO recommended that
treatment policies for countries
experiencing resistance of more than a level
of 25% to monotherapy should change to
combination therapies preferably
artemisinin-based combination therapy –
ACT

60. WHO definition of Antimalarial
Combination Therapy
• Simultaneous use of two or
more blood schizonticidal
drugs with independent
modes of action and different
biochemical targets in the
parasite: (fixed-dose
formulations or co-
administrated therapy)

61. Basis of Combination Therapy
(Multiple Drug Therapy)
• Concept is based on the synergistic or additive potential of
2 or more drugs to:
• improve treatment efficacy, and
• retard the development of resistance to the individual components of
the combination
• Concept already being realized in multiple-drug therapy
for:
• Tuberculosis
• Leprosy
• Cancer
• HIV / AIDS

62. Why Artemisinin-based combinations?
Artemisinins
• Rapid and sustained reduction of the parasite
biomass – fastest known to date
• Used for >200 yrs in China – still effective
• Rapid resolution of clinical symptoms
• Reduction of gametocyte carriage
• Duration of treatment = 2-3 days in combination
(7 days in monotherapy)
• Broad stage specificity
• No reported resistance so far

63. • Artemisinin & its derivatives:
• Artemisinine (qinghaosu) is a lactose endoperoxide
• Insoluble and can only be used orally
• Analogues have been synthesized to increase solubility and
improve antimalarial efficacy
• Most important of these are
• artesunate (water-soluble, useful for oral, i/v, i/m, and rectal
adm)
• artemether (lipid-soluble; useful for oral, i/m and rectal adm).
• Artemisin and derivatives rapidly absorbed with peak plasma
levels occurring 1-2 hrs after oral adm.
• VERY rapidly acting blood schizonticides against all human
malaria parasites
• Artemisinine has no effect on hepatic stages.

64. • Artemisinin & its derivatives:
• Mech of action:
• Production of free radicals that follows the iron-catalyzed
cleavage of the artemisinin endoperoxide bridge in the parasite
food vacuole. Arteminin and its analogues are the only drugs
reliably effective against quinine-resistant strains.
• Limited efficacy due to short plasma half-lives.
• Recrudescence rates are unacceptably high after short-course or
even 7 day of therapy
• Best used in conjunction with other agents especially those with
much longer half-lives.
• Agents with longer half lives:
• Amodiaquine
• Lumefantrine

65. Combination therapies recommended by
WHO
 Artesunate + amodiaquine
• Artemether/lumefantrine
 Artesunate + SP
 Artesunate + mefloquine
WHO Technical Consultation on
“Antimalarial Combination Therapy” – April 2001
ACTs
 Amodiaquine + SP

66. Treatment for uncomplicated malaria
Artemether-Lumefantrine (AL)
is
drug of choice.
Fixed dose contribution improves compliance. The combination is safe and
effective and has the required properties to delay the emergence of
resistance and to reduce transmission.

67. Dosage Chart for Artemether Lumefantrine
Weight (kg) Age No of
tablets/dose
5 – 14 6 mths – 3 yrs 1 tab twice x 3
days
15 - 24 4 – 8 yrs 2 tabs twice daily
x 3 days
25 - 34 9 – 14 yrs 3 tabs twice daily
x 3 days
≥ 35 > 14 yrs 4 tabs twice daily
x 3 days

68. Coartem®
• Comprises a fixed ratio of 1:6 parts of artemether and Iumefantrine,
respectively.
• Artemether – 20mg
• Iumefantrine – 120mg
• Site of antiparasitic action of both components is the food vacuole of
the malaria parasite, where they interfere with the conversion of haem,
a toxic intermediate produced during Hb breakdown, to the non-toxic
haemozoin, malaria pigment.
• Lumefantrine interferes with the polymerisation process, while
artemether generates reactive metabolites as a result of the interaction
between its peroxide bridge and haem iron. Both drugs also inhibit
nucleic acid and protein synthesis within the malaria parasite.
• The antimalarial activity of the combination of Iumefantrine and
artemether is greater than that of either substance alone.

69. Other ACTs available include:
oArtesunate (200mg) +Amodiaquine (600mg) daily for 3 days
o Artesunate + mefloquine
oDihydroartemisinin + piperaquine
oMonotherapy with artemisinin derivatives or other antimalarial
medicines are NOT RECOMMENDED.

70. Supportive Treatment of uncomplicated
malaria
For high temperature (>38.5 C)
Tepid sponging
Avoid overclothing
Paracetamol
Extra fluids and feeds

71. Follow up for uncomplicated malaria
Tell patients to return on Day 4 (a day after completing full course of
therapy)
or
Day 3 if fever persists after 2 days of starting treatment
or
Immediately if condition gets worse or signs of severe disease appear

72. Follow up for uncomplicated malariaFever persists
Ask….Did patient comply?
Do blood smear for malaria parasites
Patient complied,
blood film +ve,no clinical deterioration.. complete
treatment
blood film +ve, clinical deterioration……use alternate
antimalarial - quinine
slide –ve, asses for other cause of fever and treat
Poor compliance…supervised treatment

73. Clinical Diagnosis for severe malaria
Resources needed to confirm many of the features not
always available ; these criteria may be used
Fever or recent hx of fever AND
Presence of any sign of severe malaria
• prostration (lethargic or unconscious)
• hx of 2 or more convulsions in 24 hr period
• respiratory distress
• severe pallor
• hx of persistent vomiting
• passing dark colored urine
Irrespective of signs of alternative diagnoses

74. Clinical Assessment of Severe Malaria
• Ask for history of known clinical features of severe malaria
• Extreme weakness,
• Abnormal behaviour or altered consciousness
• Convulsions
• Drowsiness
• Time of last drink or food since the onset of illness
• Fast breathing
• Reduced urinary output
• Colour of urine
• Exclude other illnesses
• Drug history- salicylates, antimalarial drugs, herbal concoctions
• Previous illnesses
• Exclude other severe diseases e.g meningitis, diabetes mellitus, toxic encephalopathy,
septicaemia, epilepsy

75. Minimum Laboratory Investigations in
suspected Severe Malaria
• Blood film for malaria parasites
• Haematocrit and White blood cell count
• Blood sugar level
• Lumbar puncture for unconscious patients
• Urinalysis for sugar and proteins
• Electrolytes and Urea
• Blood culture
• Chest X-ray and Blood gases

76. Treatment of severe and complicated malaria
Medical emergency – SAVE LIFE!
• Requires parenteral therapy;
• IV or IM quinine depending on availability of infusion facilities
• Iv artemether
• IV artesunate
• To be followed up with a full course of oral antimalaria once patient
can take orally

77. Dosages of drugs for severe malaria
• Quinine or Artemisinin derivatives must be administered
parenterally.
• Intravenous quinine in children:
• 20mg/kg of Quinine dihydrochloride salt loading dose diluted in
10ml/kg of 4.3% dextrose in 0.18% saline or 5% dextrose over a
period of 4 hours. Then 12 hours after the start of the loading dose,
10mg salt/kg infusion over 4 hours every 8 hours until patient can
take orally.
• Change to quinine tablets 10mg/kg 8 hourly to complete a
total of 7 days treatment OR give a full dose of artemether-
lumefantrine.

78. Issues with quinine therapy
•Cardiac arrythmias
•Hypotension
•Hypoglycaemia
•Intravascular hemolysis in G6PD
deficient patients
•Risk of fluid overload

79. Artemisinin Derivatives:
• Can be used as alternatives to quinine for severe malaria
• Artesunate: - 120mg
• Artemether: - 150mg
• Alternatively, once patient can tolerate oral medication
give a full dose of artemether-lumefantrine.
• Superior to QN, few side effects
Dosages of drugs for severe malaria

80. Supportive Therapy in Severe Malaria
• Mx of the unconscious patient
• Ensure patent airway, gentle suction of nostrils & oropharynx
• Ensure patient is breathing
• Nurse in left lateral position
• Insert naso-gastric tube
• Establish IV line for drugs, blood or fluids
• Monitor blood sugar and correct hypoglycaemia
• Mx of convulsions – Ensure A,B,C
• IM Phenobarbitone 10-15mg/kg
• IV Diazepam 10mg (Adults)

81. Supportive Therapy in Severe Malaria
• Mx of severe dehydration or shock
• Mx of severe anaemia
• Blood Transfusion
• Anti-Pyretics, Antibiotics

82. Supportive Therapy in Severe Malaria
• Mx of Pulmonary oedema
• Prop patient up, Oxygen, IV frusemide 20-40mg exclude heart
failure from severe anaemia
• Mx of renal failure
• Kidney challenge
• 20mls/kg of normal saline
• Challenge with frusemide 20-40kg
• Pass catheter to monitor urinary output
• If pt does not make urine within 24 hrs
• Dialys

83. Supportive Therapy in Severe Malaria
• Nursing care – essential ‘cos patients are critically ill and need freq
monitoring
• Vital signs – pulse, temperature, resp. rate, blood pressure
• Input-Output – Strictly 24 hrs
• Level of consciousness (GCS, BCS)
• Frequent turning
• Ensure drug chart
• Neurological examination – vision, hearing
• If no facilities to monitor patient, PLS REFER!

84. Pre-referral Treatment for severe malaria
• Risk of death greatest in first 24 hours
• Therefore, in centres with insufficient facilities, patients must be referred a.s.a.p
• Pre-referral treatment must be given to avoid advanced disease, more
complications or death in transit
• Treatment options include:
• IM quinine
• IM artemether
• Im arteether
• Rectal artesunate (suppositories)

85. Dosage for rectal artesunate for acute malaria
Weight (Kg Age Artesunate Dosage
5 – 8.9 6 – 12 mths 50 mg One 50mg supp
9 – 19 12 – 42 mths 100mg 0ne 100mg supp
20 – 29 43 – 60 mths 200mg Two 100mg supp
30 – 39 6 – 13yrs 300mg Three 100mg supp
> 40 > 14yrs 400mg One 400mg supp
In the event that an Artesunate suppository is expelled from the rectum within 30 minutes of insertion, a
second suppository should be inserted.

86. MALARIA CHEMOPROPHYLAXIS
This is not recommended for people living in areas of stable malaria.
However, people with sickle cell anaemia and non-immune visitors are
expected to be on regular chemoprophylaxis.
Sickle cell anaemia:
The recommended chemoprophylaxis is proguanil 100mg daily for
children up to 15 years and 200mg daily for adults.
Non-immune Visitors:
The recommended chemoprophylaxis will be available in the visitor’s
country of origin, however, the following options: mefloquine, doxycycline,
atovaquone-proguanil are available. Doses should be taken prior to arrival
in Nigeria and continued during the stay and following departure from the
country.

87. • It is the preventive treatment of malaria that target not only the blood
stages but also the initial liver stages of malaria.
• It is the modality of treatment for most travellers and the user can stop
taking the drug 7days after leaving the area of risk.

88. • Doxycycline 100mg daily : started a day before travels and continue
for 4wks thereafter.
• Mefloquine 250mg once a week started 2wks before travels and
continue 4wk thereafter.
• Malarone (atovaquine/ proquanil) 1 tab dly started one day before
travel and continue 1 wk after returning.
• Regime depends on person who is to take the medication and country
or region travelled.
• Dosages depends on what is available in the area

89. Prognosis
• Good, if appropriate treatment is started early
• Post malaria neurological syndromes may occur
• Seen in 10% of children following cerebral malaria
• Hemiparesis
• Hemi – sensory deficit
• Hemianopia
• Cortical blindness
• Diffuse cortical damage
• Tremor
• Cranial nerve palsies
After six months, 50% of these patients recover completely,
and 25% recover partially, the remainder don’t recover.

90. Malaria Control Strategies
ROLL BACK MALARIA INITIATIVE
• A partnership involving governments, private sector,
research organizations, civil society, media,
development partners.
• Aims to reduce malaria by half by 2010.
• Historic Summit in Abuja, April 25, 2000 (Abuja
Declaration and targets)

91. RBM Strategies
• Effective Case Management
• Multiple Disease Prevention
• IPT (not applicable to children)
• ITNs
• Integrated Vector Management
• Chemical control
• Biological control
• Environmental control

92. Malaria prevention• Anti-vector measures
• Community
• Environmental hygiene/control
• Windows and door nets
• Indoor residual spraying
• Personal
• Protective clothing
• Insect repellant creams
• Plain bed nets
• Insecticide treated nets (impregnated with pyrethrium or
permethrin)
• Chemoprophylaxis – for sickle cell patients, non-immune visitors

93. CHEMICAL CONTROL
Indoor Residual Spraying (IRS):
• Involves coating the walls and other surfaces of a house with a
residual insecticide.
• Insecticide kills mosquitoes and other insects that come in
contact with these surfaces for several months.
• Does not directly prevent people from being bitten by
mosquitoes; usually kills mosquitoes after they have fed if they
come to rest on the sprayed surface.
• Prevents transmission of infection to other persons.
• To be effective, IRS must be applied to a very high proportion
of households in an area usually about 80%.
• Pilot Indoor Residual Spraying (IRS) carried out in Barki Ladi
area of Plateau state, north central of Nigeria.

94. BIOLOGICAL CONTROL
• Include toxins from the bacterium Bacillus thuringiensis var. israelensis (Bti). Very
specific, affecting only mosquitoes, black flies, and midges.
• Insect growth regulators such as methroprene. Methoprene is specific to
mosquitoes.
• Mosquito fish (Gambusia affinis) are effective in controlling mosquitoes in larger
bodies of water.
• Other potential biological control agents, such as fungi (e.g., Laegenidium
giganteum) or mermithid nematodes (e.g., Romanomermis culicivorax), are less
efficient for mosquito control and are not widely used.

95. ENVIRONMENTAL CONTROL
Breeding sites:
• large bodies of fresh water
• small collection of seepage and stagnant water,
• rice fields,
• plant hollows and cavities,
• man-made containers e.g. wells, storage tanks, disused utensils, tins
• coconut husks
• Fences (with broken bottles)
• Overhead tanks etc.
• Construction sites

96. ENVIRONMENTAL CONTROL
• Improve proper drainage
• Sand-filling and grading of pot holes
• Clearing vegetation
• Destroying water holding plants
• Disposal of disused tyre, utensils, coconut husks etc by
burning, burying or smashing
• Periodic flushing of carnal, wearing of protective clothing

97. TYPES OF ITNs Retreatable ITNs: Introduced in the 1980s.
 Insecticide action lasts for maximum of 9 months.
 Long-Lasting Treated Nets
Polyethylene and polyester, polyethylene longer lasting up to about
5yrs, effective after 20 washings,
ready to use, reduced human exposure
• Kill or repel mosquitoes
• Prevent physical contact with mosquitoes
• Kill or repel other insects:
• Lice
• Ticks
• Bedbugs
• Cockroaches

98. MALARIA VACCINE
Vaccines for malaria are under development, with no completely
effective vaccine yet available. The first promising studies
demonstrating the potential for a malaria vaccine were performed in
1967 by immunizing mice with live, radiation-attenuated sporozoites,
providing protection to about 60% of the mice upon subsequent
injection with normal, viable sporozoites.
Since the 1970s, there has been a considerable effort to develop
similar vaccination strategies within humans. It was determined that an
individual can be protected from a P. falciparum infection if they
receive over 1000 bites from infected, irradiated mosquitoes.

99. The first vaccine developed, that has undergone field trials, is the SPf66 developed
by Manuel Elkin Patarroyo in 1987. It presents a combination of antigens from the
sporozoite (using CS repeats) and merozoite parasites. During phase I trials a 75%
efficacy rate was demonstrated and the vaccine appeared to be well tolerated by
subjects and immunogenic. The phase IIb and III trials were less promising, with the
efficacy falling to between 38.8% and 60.2%. A trial was carried out in Tanzania in
1993 demonstrating the efficacy to be 31% after a years follow up, however the most
recent (though controversial) study in the Gambia did not show any effect. Despite the
relatively long trial periods and the number of studies carried out, it is still not known
how the SPf66 vaccine confers immunity; it therefore remains an unlikely solution to
malaria.
The CSP was the next vaccine developed that initially appeared promising enough to
undergo trials. It is also based on the circumsporoziote protein, but additionally has the
recombinant (Asn-Ala-Pro15Asn-Val-Asp-Pro)2-Leu-Arg(R32LR) protein covalently bound
to a purified Pseudomonas aeruginosa toxin (A9). However at an early stage a complete
lack of protective immunity was demonstrated in those inoculated. The study group
used in Kenya had an 82% incidence of parasitaemia whilst the control group only had
an 89% incidence. The vaccine intended to cause an increased T-lymphocyte response
in those exposed, this was also not observed.

100. CONCLUSION
Malaria still kills an unacceptable number of African
children each year, and blights the life of many millions
more. Recent scientific advances now make it possible
to dramatically reduce this burden.
It will require an enormous financial, technical, and
political commitment to reduce the number of childhood
malaria deaths in Africa from the current level of one
every 30 seconds.
At the start of the 21st century, there is unprecedented
political momentum to carry this challenge forward. It
will be well worth the effort.