Clinical Aspects of Malaria

1. Clinical Aspects of
Malaria
Part 2

3. Relapse and recrudescence
It is the disease’s potential for long persistence.
Relapse
P. vivax (more important in Asia) and P. ovale( Africa).
Primaquine will eradicate hypnozoites in over 80% of
cases, but if not given relapse occur in more than 50%
of cases.
Recrudescence
Applies to a recurrence of malaria from surviving blood
merozoites.
Due to failure of treatment to eliminate the asexual
erythrocytic parasites.
Recrudescence is characteristic of P. falciparum
infection but lesser in other malaria.
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8. Severe Malaria
Death from acute P. vivax, P. ovale, or P. malariae
infection is very rare, following ruptured spleen
traumatic or spontaneous).
Falciparum malaria is a potentially lethal infection
with rapid progression to severe disease.
Young children present with cerebral malaria in less
than one day
Rare in malnourished children, strike healthiest
people.

9. WHO definition of severe malaria (clinical)
1. Cerebral malaria with unrousable coma persisting at least 30
minutes after generalized convulsions.
2. Severe anaemia.
3. Renal failure .
4. Pulmonary oedema or adult respiratory distress syndrome.
5. Hypoglycemia
5. Circulatory collapse or shock-hypotension ( Algid Malaria )
6. Spontaneous bleeding from gums, nose, gastrointestinal tract
etc. and/or substantial laboratory evidence of DIC.
8. Repeated generalized convulsions, more than two in 24 hours
despite cooling.
9. Acidaemia.
10 .Macroscopic haemoglobinuria.
One or more of the above features in the presence of
asexual parasitaemia define severe falciparum malaria.

10. Cerebral Malaria
Defined strictly as unrousable coma ( no response to
painful stimuli) in falciparum malaria.
The most prominent feature of severe malaria.
The onset of coma may be sudden after generalized
seizure, or gradual.
Extreme agitation is poor prognostic sign.
Prodromal history, usually several days in adult and
6 - 12 hours in children, with history of convulsions.

11. .On examination Severe Malaria Cont.
1. Patient febrile and unrousable.
2. Passive resistance to hand flexion.
3. Patient usually warm, dry, well perfused peripherally.
4. The clinical features are of symmetrical encephalitis.
Gaze is usually normal or divergent.
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Untreated cerebral malaria is fatal and the overall
mortality of treated malaria 15% in children, 20 % in
adults and 50% in pregnancy.
Other manifestation of CNS dysfunction:
Delirium and brief reactive psychosis.
Cerebellar syndrome:
Cerebellar ataxia
(Defective muscular control resulting in irregular and jerky movements)

12. Anaemia
Normocytic anaemia ( Hct <15% or Hb <5 g/dl)).
It is a big problem in children, may lead to high
output cardiac failure and sudden death.
Acute renal Failure
A common complication of malaria in adults living in
areas of low or unstable transmission.
Associated with haemoglobinuria in patients with
massive haemolysis ( B. W. F. )

13. Metabolic Acidosis
May result from renal failure in adults, but usually
there is a primary ( type B) lactic acidosis.
Blackwater fever
Due inadequate quinine treatment.
In the first half of the twentieth century mortality rate
was high, half of which is due renal failure.
Today, the mortality is much lower.
Mortality is highest when associated with severe
malaria or other vital organs dysfunction.

15. Acute Pulmonary oedema
It is one of the form of adult respiratory distress
syndrome.
Result from sudden increase in pulmonary capillary
permeability.
Hyperventilation or kussmaul’s breathing is a poor
Prognostic sign in malaria. It is associated with
metabolic acidosis, pulmonary oedema or pneumonia.
May develop at any time in severe falciparum malaria, it
is common in pregnant women.

16. Algid Malaria (Hypotension)
Patient with severe disease may develop sudden
hypotension and become shocked. This is called
‘algid malaria’
Shock usually responds temporary to saline infusion
and inotropes, but pulmonary oedema may develop if
too much salt is given.
Overall mortality is high.

17. Hypoglycemia
Either asymptomatic in severely ill patient. Or
present as a further deterioration in the level of coma.
Whole blood glucose less than 2.2 mmol/l or 40 mg/dl.
Occur in 8% of adults and 30% of children.
In pregnant women with quinine-induced hypoglycemia:
1. The clinical features are usually evident.
2. Patient respond dramatically to glucose.

18. Malaria In
Children
Severe falciparum malaria is rare in infancy, but of
high mortality.
Majority present with fever and malaise, respond
rapidly to antimalarial treatment.
In young children the progression of falciparum
malaria can be rapid.
General seizures are more common in P. falciparum

19. Severe malaria
Manifestations:
- Coma. - Convulsion ( <3-year age group).
- Lactic acidosis. - Hypoglycemia and
- Severe anaemia.
Rare in older children.
Intense transmission areas: Profound anaemia,
(1-3 years ).
Less stable transmission areas : predominantly Cerebral
malaria.
Children tolerate anti-malarial drugs better than adults,
resolve more quickly.

20. A 3-year-old Gambian girl
with cerebral Malaria and
opisthotonos
A 6-year-old Thai boy
with cerebral Malaria.
His father was admitted
at the same day with
cerebral Malaria - both
survive

21. Malaria in Pregnancy
A. In areas of intense Transmission
The principle impact of falciparum malaria in
pregnancy are :
1. An increased incidence of anaemia.
2. Reduction in birth weight of babies born to
primigravidae.
Despite intense sequestration of parasites in placenta
the mother is usually asymptomatic.

22. B. In areas of less transmission
If pregnant women develop severe malaria:
1. Fetal loss is common, Abortion, premature labor.
2. Maternal mortality is also high.
3. Pulmonary oedema and hypoglycemia are particular
complication.
The mortality of cerebral malaria in pregnancy is high.
Congenital Malaria
Rare, even the risk of symptomatic malaria is low (<1%).
More common in non-immune mothers than highly
immune ones.
Babies present with anaemia, jaundice, and
splenomegaly.

23. DIAGNOSIS
There are no diagnostic clinical features of malaria
except fore the regular paroxysm with virtual
asymptomatic interval in endemic regions.
In endemic areas , in any febrile illness, malaria should
be excluded.
Blood smear:
Malaria is diagnosed by microscopic examination of
thick (parasites) and thin (species) blood films stained
by any Romanovsky's stain.
The red cells in the tail of the film should be examined
under oil immersion.
The level of parasitaemia is expressed as the number of
parasitized RBCs among 1000 cells and this figure is
converted to the number of parasitized RBCs per l.

24. Other Techniques
• Quantitative Buffy Coat (QBC) Technique
Blood samples are taken into a specialized capillary
tube containing acridine orange stain and a float.
Under high centrifugal forces (14000) the infected
RBCs, which have a higher buoyant density than
uninfected RBCs, become concentrated around the
float. The acridine orange fluorescence from malaria
parasites can be visualized under ordinary
microscope.

25. Chronic complications of Malaria
Hyperactive Malarial splenomegally
Widely known as Tropical splenomegally Syndrome.
Occurs in areas of intense transmission , throughout the
tropics, the highest incidence is in Papua New Guinea.
Chronic or repeated infections lead to an abnormal
immune response, characterized by:
1. Gross splenomegaly, with normal architecture.
2. Lymphocytic infiltration of hepatic sinusoids
with Kupffer cell hyperplasia (Hepatomegally).

26. In many cases no malaria parasite in peripheral blood.
Treatment
Splenectomy is only recommended if there is failure
of prophylaxis given for at least 6 months and there
is severe hypersplenism.
Quartan Malarial Nephropathy
Chronic or repeated infection with P. malariae may
cause soluble immune-complex injury to the renal
glomeruli, resulting in the nephrotic syndrome in
children.
Subendothelial deposits of complement and immuno-
globulines , often P. malariae antigens.

27. Treatment
Aim of treatment
1. Causal or true prophylaxis:
Use of drugs that can act on tissue stages in the liver ( Tissue
Schizontocidal drugs).
2. Radical cure ( Anti-relapse):
Use of drugs that can act on latent forms in the liver
(Hypnozoitocidal drugs).
3. Temporary cure (Clinical cure) &
Suppressant treatment:
That is a drug given as prophylactic, but acts
through eliminating the erythrocytic forms as
they invade the RBCs; no action being exerted on
P. E. forms.
4. Control: Gametocidal drugs.

28. Antimalarial drugs
Antimalarial drugs are more toxic than antibacterials, but with
rare serious adverse effects
Fall in three broad groups
1.The quinoline-related compounds: ( inhibit Haem
polymerization):
- Quinine. - Quinidine.
- Chloroquine - Amodiaquine.
- Mefloquine. - Halofantrine
- Primaquine.
2.The antifols: ( interfere with folic acid synthesis):
- Pyrimethamine. - Proguanil.
- Chlorproguanil. - Trimethoprim.
3. The artemisinin compounds: ( involve oxidative damage):
- Artemisinin. - Artemether.
- Artesunate.

29. Several antibacterial drugs have antiplasmodial
activity, although slow , can be used in combination with
other antimalarial drugs:
- Sulfonamides - sulphones .
- The tetracyclines. - The macrolides.
Tetracycline, in multi-drug-resistant parasites.
Antimalarial treatment must usually provide
therapeutic drug concentration for 7 days to effect a
cure in non immune subjects.
In semi-immune subjects the host defense collaborate
with the antimalarial treatment to eradicate residual
parasites, and a short course of treatment is effective.

30. P. Vivax
Adult treatment.
Based on Chloroquine tablets containing 150mg base.
Day 1 4 tablets (600mg base) or 10 mg/kg first dose.
2 tablets (300mg base) or 5 mg/kg 6-8 hours later.
Day 2 2 tablets (300mg base) or 5 mg/kg.
Day 3 2 tablets (300mg base) or 5 mg/kg.
Next 14 days primaquine 2 tablets (each tablet contains 7.5mg
base daily with food ).

31. P .falciparum.
Uncomplicated malaria (where patients can take oral therapy) can
usually be treated effectively with one of three regimens:
1. Quinine sulphate 10 mg salt/kg 8 hourly for seven days plus
doxycycline 100 mg daily for 7 days. Tetracycline (4mg/kg daily for
seven days) or the combination drug FansidarTM (25mg/kg
sulfadoxine plus 1.25mg/kg pyrimethamine as a single dose) can be
given as less expensive alternatives to doxycycline.
2. MalaroneTM (atovaquone 250 mg plus proguanil 100 mg) 4 tablets
daily for three consecutive days. This combination therapy is
relatively new and appears to be very effective but it is also very
expensive.
3. Mefloquine (LariumTM) given as 15 mg/kg in a divided dose
followed by 10 mg/kg the following day. Antipyretic and antiemetic
agents may need to be given prior to mefloquine administration to
reduce the risk of vomiting..

32. Severe malaria
In patients who have not received quinine in the previous 48 hours,
one of two regimens can be used:
1. Quinine dihydrochloride 20 mg salt/kg base given i.v. in 5% w/v
dextrose or normal saline as a once-only 4 hour infusion
followed, 4 hours later, by quinine dihydrochloride 10 mg salt/kg
base 4-hour infusions, 8 hourly.
2. Where a syringe pump or other accurate infusion device is
available, quinine dihydrochloride 7 mg salt/kg base over 30
minutes followed immediately by quinine dihydrochloride 10 mg
salt/kg base over 4 hours then, starting 4 hours later, quinine
dihydrochloride 10 mg salt/kg base as 4 hour infusions, 8 hourly.

37. Thank You

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