How to manage it

1. Malaria-
Parasitology,
pathogenesis,
clinical features,
and treatment
Department of Internal Medicine
Dr M.KATASO
Infectious Unit

2. Learning objectives
At the end of this session, learners should be able to do the following:
• Know the Plasmodium spp associated causation of malaria.
• Understand basic parasitology of Malaria
• Understand the pathogenesis of Malaria
• Be familiar with clinical features Malaria
• List features of complicated Malaria
• List common laboratory and imaging investigations for Malaria.
• Be familiar with principles of managing Malaria.

3. Introduction
• Malaria is a protozoa infection of the genus Plasmodium.
• It is transmitted through the bite of an infected female mosquito belonging to the genus
Anopheles (An.).
• In Zambia, there are three species that can transmit human malaria: An. gambiae, An.
arabiensis, and An. funestus.
• They differ from many other mosquitoes common in Zambia by being late-night feeders.
• Five species of Plasmodium (P.) parasites cause infections in humans: P. falciparum, P. vivax, P.
malariae, P. ovale, and P. knowlesi .
• The most common species that is clinically significant and causes the most lethal form of
malaria is P. falciparum.
• In Zambia, P. falciparum accounts for more than 95% of malaria cases

4. Malaria parasite life cycle
• Malaria parasite cycle comprise
3 cycles, namely:
oSporogonic cycle
oExoerythrocytic cycle
oErythrocytic cycle

5. • Exoerythrocytic cycle occurs in the Liver producing a schizont containing immature merozoites.
• Erythrocytic cycle happen in RBCs, Giving rise to mature trophozoites and gametocytes.
• Sporogonic cycle occurs in the Mosquito forming oocysts containing sporozoites
• The female Anopheles mosquito ingests gametocytes when it feed on blood of infected
individual.
• Gametocytes mature through stages Macrogametocytes→Ookinete→Oocyte→Sporozoites.

6. • Sporozoites are transmitted to uninfected individual through a mosquito bite.
• Sporozoites enter the exoerythrocytic cycle in the liver to produce schizonts containing
merozoites.
• Schizonts rupture releasing merozoites which enter the Erythrocytic cycle in RBCs.
• In malaria caused by P. vivax and P. ovale, but not P. falciparum, some parasites remain in the
liver forming hypnozoites can cause a relapse of the disease long after treatment of the blood
stage infection.
• Merozoites transform into immature trophozoites(ring form stage) and eventually mature
trophozoites and gametocytes in RBCs.
• Gametocytes enter the sporogonic cycle once again after a mosquito bite and cycle repeats its
self.

7. Pathogenesis
• Infection in humans happens when a female Anopheles species mosquito inoculates Plasmodia
sporozoites into the blood system while feeding
• The parasite then moves to the liver, where it enters a hepatocyte and develops.
• It enters the blood stream from the liver and multiplies inside the red blood cells.
• Capillaries occlusion occurs in major organs resulting in organ dysfunction.
• P. falciparum is especially lethal as it invades red blood cells of all ages making the infection
difficult to be destroyed by the human immune system.
• .

8. • P. vivax and P. ovale invade only young reticulocytes
• P. falciparum has a natural affinity for soft tissues.
• This causes it to undergo sequestration in the brain, kidneys, and blood vessels.
• P. falciparum is thus associated with:
o Extremely high levels of parasitaemia
o Pronounced anaemia
o Cerebral malaria.
• Drug resistance to P. falciparum has also been shown to develop faster than with other
Plasmodium strains

9. Pathogenesis of Cerebral Malaria(CM)
• P. falciparum induces cytoadherence to vascular endothelium of RBCs containing the mature
forms of the parasite.
• Cytoadherence causes sequestration of parasitized erythrocytes in the microcirculation, mainly
capillaries and post-capillary venules.
• Sequestration and hyperparasitaemia are prominent in cerebrum, cerebellum as well as the
medulla oblongata
• The high molecular transmembrane protein P. falciparum erythrocyte membrane protein 1
(PfEMP1) is the most important ligand for cytoadherence.
• Under febrile conditions, there is enhanced expression, PfEMP1 mediated cytoadhesion.

10. • On the vascular endothelium numerous receptors that can bind PfEMP1 have been identified.
• The intercellular adhesion molecule 1 (ICAM-1) is the most important receptor on brain
endothelium, and its expression is upregulated by the pro-inflammatory cytokine TNF

11. Clinical Features
• Malaria may manifest clinically either as an acute uncomplicated disease or as severe malaria.
• Incubation period of malaria ranges from 10 to 14 days depending on the parasite species.
• Relapse occurs when parasites persisting in the liver reinvade the bloodstream (this is common
with P. ovale and P. vivax.
• P. falciparum malaria is characterized by fever, which may be continuous, recurring, or
irregular.
• Clinical manifestations may be categorized into symptoms of uncomplicated malaria and those
of severe malaria.

12. Uncomplicated Malaria
• Early symptoms are usually non-specific and are often characterized by intermittent febrile
illness.
• Fever is the most common symptom.
• Other symptoms include:
oHeadache
oAching joints
oBack pain
oNausea and vomiting
oGeneral discomfort usually accompany fever
• Possibility of other infections, either co-existing with malaria or as the sole cause of fever,
should always be borne in mind when determining the diagnosis.

13. Complicated Malaria
• P. falciparum infection in the presence of any life-threatening condition is considered as severe
malaria.
• Some of the life-threatening conditions include signs and symptoms such as:
oCerebral malaria, defined as coma not attributable to any other cause in a patient with P.
falciparum malaria
oGeneralized convulsions (more than two episodes within 24 hours)
oComa or altered level of consciousness
oDrowsiness or lethargy

14. oProstration (inability to sit or stand without support)
oAcute pulmonary oedema (adult respiratory distress syndrome)
oHypotension and shock
oPersistent/excessive vomiting
oDIC manifesting as spontaneous or prolonged bleeding from puncture sites
oFluid and electrolyte disturbances
oAcute renal failure
oJaundice

15. Laboratory indicators of severe malaria may include the following:
1. Hyperparasitaemia (proportion of parasitized red cells >5% in the non-immune and
>10% in the semi-immune population)
2. Acidosis (metabolic) (plasma bicarbonate <15 mmol/L)
3. Severe normocytic anaemia (haemoglobin (Hb) <5g/dl or packed cell volume [PVC] <
15%)
4. Hyperlactataemia (lactate >5 mm)
5. Haemoglobinuria
6. Renal impairment (creatinine >265 μmols/L)
7. Hypoglycaemia (blood glucose <2.2 mmol/L)

16. Signs and
symptoms of
Malaria
UNCOMPLICATED MALARIA SEVERE AND COMPLICATED MALARIA
Fever
Headache
Sweats and chills
Body pains
Acute gastroenteritis
Nausea
Severe anaemia (Hb <5 g/dl)
Jaundice
Drowsiness
Convulsions
Respiratory distress
Unconsciousness/coma
Altered mental state
Hyperparasitaemia
Prostration (i.e., generalized weakness, inability to
stand or walk)
Abnormal bleeding
Dehydration
Hepatomegaly
Splenomegaly

17. Diagnosis
• Diagnosis of malaria should be based on parasitological confirmation (laboratory).
• A complete history should include:
o Common symptoms of malaria,
o Age
o Place of residence,
o Recent history of travel
o Past medical history
o Drug history
• Parasitological confirmation (laboratory) is done by examining either a blood smear/slide or
malaria RDT.
• RDTs detect antigens derived from malaria parasites in lysed blood.

18. Supportive Investigations
Additional lab tests that may be indicated to assess severity of malaria include:
• Haemoglobin
• Blood glucose estimation ( in patients with altered consciousness)
• Prothrombin time
• Bilirubin
• Urea and creatinine
• Chest X-ray
• Full blood count

19. Investigations for differential diagnosis:
• Lumbar puncture to exclude meningitis
• Blood culture
• Urine examination
• Chest X-ray

20. Treatment
Treatment options depend on disease severity.
Uncomplicated Malaria
• First-line treatment of uncomplicated malaria in Zambia is artemether-lumefantrine (AL) given
over three consecutive days.
• Alternative first-line treatment is dihydroartemisinin/ piperaquine, given as a three-day oral
treatment.
• Supportive care for patients with hyperpyrexia (38.5°C and above) include paracetamol or
aspirin every 4 to 6 hours (maximum 4 doses in 24 hours) until symptoms resolve.

21. Severe Malaria
• Severe malaria is a medical emergency.
• Injectable artesunate is the drug of choice.
• Artemether (IM) or quinine (IV/IM) are recommended alternatives.
• Once patient is able to tolerate oral therapy treatment should be changed an effective oral
antimalarial using such as artemether-lumefantrine.
• Artesunate is dosed at 2.4 mg/kg body weight IV or IM given on admission (time = 0), then at
12 h and 24 h, then once a day.
• There should be an interval of at least 8 hours between the last dose of artesunate and the first
dose of artemether/lumefantrine.

22. • Quinine is given at a loading dose of 20 mg/kg body weight (maximum 1200 mg) in10%
dextrose as alternative.
• After 8 hours, give a maintenance dose of 10 mg/kg body weight (maximum 600 mg) over 4
hours, repeated every 8 hours until patient can swallow or after coma resolution.
• Oral quinine 10 mg/kg body weight is then given every 8 hours to complete a 7-day course of
treatment.

23. Management of complications
Hyperpyrexia
• Treat with appropriate antipyretic such as Paracetamol or Aspirin.
Seizures
• Diazepam at 10mg as a slow injection
• Phernobarbitone at 10–15 mg/kg IM injection is the best treatment for repeated convulsions
Hypoglycaemia
• 50% Dextrose at 1ml/kg followed by 10% Dextrose as maintenance
Severe Anaemia
• Blood transfusion should be considered if the haematocrit falls below 15% or haemoglobin
concentration is < 5 g/dl.

24. Malaria Prophylaxis
• Malaria prophylaxis should be used in sickle cell disease patients and in non-immune visitors
because of risk for severe disease.
• In SCA recommended prophylaxis is Deltaprim (Maloprim),a combination tablet containing
pyrimethamine and dapsone used for malaria prophylaxis.
• It is given at a dosage of 25 mg pyrimethamine and 100 mg dapsone tablet taken once per
week, preferably in the morning.
• For visitors to (non-immunes) to Zambia ,options include mefloquine, atovaquone-proguanil,
and doxycycline.
• Doses should be taken prior to arrival in Zambia, continued during the stay, and continued
following departure from Zambia
• Visitors are encouraged to use other effective protective measures such as the use of insecticide-
treated nets (ITNs),

25. References
• Guidelines for the Diagnosis and Treatment of Malaria in Zambia,4th edition.
• Dondorp AM;Pathophysiology, clinical presentation and treatment of cerebral malaria;
Neurology Asia 2005; 10 : 67 – 77

26. END!!!!!
Questions???