General Medicine

1. Malaria
Natangwe Shimhanda
201208214

3. Epidemiology

4. • Its mostly Endemic but pandemics may also
occur
• In Southern Africa its endemic in Angola,
Mozambique, Malawi, Northern Namibia,
Northern Botswana, some areas of Zimbabwe
and South Africa

5. Aetiology
• Malaria is a vector borne protozoan infection
caused by a parasite of genus Plasmodium.
• Four sp known to cause Malaria: P. Vivax; P.
Ovale; P. Malariae; P. Falciparum
• All four species exist in southern Africa
• Transmitted by the bite of Anopheles
mosquitoes to nourish its developing eggs

7. Types of Malaria

9. Life Cycle

10. Effect on Treatment
• P. Vivax ; P. Malariae; P. Ovale may re-enter the
liver and continue to multiply long after the
initial bloodstream invasion has ceased.
• This may result in relapse of malaria e.g. P.
Malariae can relapse as long as 40 yrs after
the initial infection
• P. Falciparum doesn’t have an exo-erythrocytic
cycle

11. Clinical manifestations
• Virulence depends on the immune status of
the host
• Innate immunity occurs in people with G6PD,
Sickle Cell Trait and absence of the DUFFY
antigen in RBCs.

12. Resistance and immunity
• The intraerythrocytic development of P. falciparum is inhibited in
persons with various hemoglobinopathies.
• Persons with G6PDD are more sensitive to certain antimalarials
(quinine, 8-aminoquinoline).
• Persons lacking the Duffy blood group antigen are resistant to P.
vivax, but susceptible to P. ovale.
• A milk diet partially inhibits the development of malarial parasites
in the RBCs because of a resulting reduced supply of p-
aminobenzoic acid (vitamin H1). This results in a milder malarial
course, e.g., in infants.

13. Clinical manifestations
• The Plasmodium species with the most pronounced
pathogenicity is Plasmodium falciparum, whereas the
other Plasmodium species cause milder
• Onset symptoms. Malaria begins with nonspecific
initial symptoms that last several days:
headache,
muscle and joint pains,
general fatigue, chills,
occasionally nausea, intermittent fever, either continuous
or at irregular intervals.

14. Classic malarial paroxysm
• After an initial rise in temperature, peripheral
vasoconstriction causes a period of chills (lasting for
about 10 minutes to one hour), then the temperature
once again rises to 40–41 °C, whereupon peripheral
vasodilatation and an outbreak of sweating follow.
• These bouts occur mainly in the afternoon and evening
hours.
• Once the paroxysm has abated and the fever has fallen,
the patient feels well again until the next one begins.
• In severe malaria tropica, however, circulatory
disturbances, collapse, may occur without fever (algid
malaria).

15. Complicated Malaria
• If any of the symptoms is present, make a diagnosis of
severe malaria and treat as an emergency:
Cerebral malaria (unarousable coma)
Severe anaemia (<5g/dl)
High Parasitemia
Renal failure (oliguria/anuria)
Pulmonary edema
Circulatory collapse
Hypoglycemia
DIC
Severe metabolic acidosis
Repeated generalized seizures

16. Nerological:
Coma; Hypoglycaemia;
Seizures; Opisthotonus;
Cranial nerve palsies
Respiratory:
Pulmonary oedema;
Secondary bacterial
pneumonia
CVS:
Shock; Cardiac failure (algid
malaria); Dysrhymias with
quinine
Renal:
Acute renal failure;
hemoglobinuria
Abdomen:
Hematological:
Severe anaemia (<5g/dl);
High parasitemia > 2%; DIC;
Thrombocytopenia

17. Course of infection and recurrence.
• The malarial paroxysms are repeated at intervals until parasite
multiplication in the erythrocytes is suppressed by
chemotherapy or the host immune response.
• Parasites that persist in the host can cause relapses for
months or even years after the initial infection.
• Recurrence results either from persistence of erythrocytic
forms reactivation of hypnozoites (relapse).

18. Pathogenesis
• The clinical manifestations of malaria are
caused by the erythrocytic stages of the
plasmodia and reflect multifactorial
pathogenic process affecting many different
organs.

19. The role of cytokines
• As a result of erythrocytic schizogony and the attendant rupture of
erythrocytes, malarial antigens (phospholipids and glycolipids) are
released that stimulate macrophages and monocytes to produce tumor
necrosis factor alpha (TNFa) and other cytokines (IL-1, IL-6, IL-8).
• Cytokine production is also initiated by IFNc produced in the
immunological TH1 response.
• TNFa plays a special role in pathogenicity, since the concentration of this
cytokine in the blood correlates with the severity of a P. falciparum
infection.
• This substance also, at higher concentrations, induces fever, inhibits
erythropoiesis, stimulates erythrophagocytosis, and causes various
nonspecific symptoms such as nausea, vomiting, and diarrhea.
• At lower concentrations, TNFa can contribute to the killing of the
intracellular parasites. Various other cytokines either synergize with TNFa
or induce different reactions.

20. Other processes
• Due to the destruction of RBCs and parasites and resulting production of
TNFa, phagocytosing cells of the reticuloendothelial system are activated.
• Signs of this include splenic swelling in the course of the infection and
increased elimination of erythrocytes in the spleen.
• Renal damage in acute malaria tropica is caused by capillary
cytoadherence and tubular necrosis. In malaria quartana, such damage is
due to deposition of immune complexes in the renal capillaries.

21. Pathological changes
• Brain capillaries are clogged with infected RBCs (the
pigment in the plasmodia is especially noticeable),
hemorrhages, necrotic foci on obturated vessels
surrounded by inflammatory reactions.
• Further changes can be found in the spleen and liver
(for instance swelling, hyperplasia of phagocytosing
cells containing plasmodia and pigment), heart,
lungs, kidneys, and other organs.

22. The Sickle cell trait

23. Diagnosis
• Detection of malarial parasites in the blood.
• Stages of P. falciparum, P. vivax, and P. ovale can be found in blood five to
eight days after the infection at the earliest, P. malariae not until after 13–
16 days.
• Rapid tests (ParaSight, MalaQuick, RDTs) have also been available for some
years to diagnose P. falciparum infections.
• Using a monoclonal antibody, these tests can detect a specific
Plasmodium antigen (HRP2) in whole blood with a very high level of
sensitivity and specificity.
• Another rapid test (OptiMAL) for diagnosis of all Plasmodium species is
based on detection of specific lactate dehydrogenase.

28. Therapy
• Patients infected for the first time may suffer
highly acute and severe courses of malaria.
• Therapy and intensive clinical monitoring must
therefore begin immediately, especially in
acute malignant tertian malaria

29. Treatment of acute disease
• The clinical symptoms of malaria are caused by the asexual
forms in the erythrocytic schizogonic cycle. A clinical cure is
thus achieved by eliminating these forms or stages with so-
called schizonticides.
• The antimalarials preferred in this indication are fast-acting
schizonticides such as quinine, mefloquine, and halofantrine
(in most countries artemisinin based therapy ACT) as well as
quinine combined with doxycycline (especially in complicated
tropical malaria) and various combined preparations.

30. Treatment of uncomplicated Malaria
• Oral therapy: A combination of an atimalarial and
artemenisinin.
• CoArtem (artemether20/lumefantrine120)
• 0 hrs, 8 hrs, 24hrs, 36hrs, 48hrs and 60 hrs
• Artmether should be avoided in early pregnancy
Weight Dose
5 - 14.9kg 1 tablet B.D *3
15 – 24.9kg 2 tablet B.D *3
25 – 34.9kg 3 tablet B.D *3
adult 4 tablets B.D *3

31. Treatment of Complicated Malaria
tropica
• IV quinine was a drug of choice
• Loading dose of 20mg/kg in 5% DD over 4 hours
• Followed by 10mg/kg every 8 hours until the
patient can take oral quinine if they’re not
vomiting
• If IV access is not possible: give IM 10mg/kg at 0
hours, 4 hours and then 12 hourly
• Give specific supportive treatment for
complications

32. Quinine complications
• QT prolongation  dysarhythmias
• Methemoglobinemia
• Hemolysis in G6PDD
• HYPOGLYCAEMIA
• THROMBOCYTOPENIA

33. Artesunate
• 2.4 MG/KG IV/IM AT 0, 12 HOURS, 24 HOURS
then daily for 7 days
• When patient has recovered, 2mg/kg of oral
artesunate OD
• Adverse effects (uncommon)
• Cardiotoxicity in high doses
• Drug induced fever
• Skin rash

34. Prophylaxis
• Malarone ( Atovoquine250/proguanil
hydrochloride100) taken once daily with food
as prophylaxis. Should be started 2 days
before travelling and continued for 7 days on
return.
• For paediatrics you give a dose Atovoquine
62.5mg/ proguanil hydrochloride 25mg

35. Prevention
• mosquito bite prevention,
• chemoprophylaxis,
• emergency stand-by therapy.

36. References
• https://www.sciencedaily.com/releases/2011/
04/110428123931.htm
• Wittenberg D.F. (2009), Coovadia’s Paediatrics
and Child Health. Oxford University Press
Southern Africa (pty) Ltd
• J. Alastair, 2016. Davidson’s Essentials of
Medicine, 2nd ed. Churchill Livingstone Elsevier
(pty)
• 2016, WHO Malaria guidelines