this lecture will help students from any medical field to learn more about the five species of Plasmodium Malaria, the clinical presentation of malaria, various strategies of malaria diagnosis, management of both complicated and non-complicated malaria, and management of malaria during pregnancy according to the recommendation of WHO. https://www.youtube.com/watch?v=Tmk71zeydbw&t=12s

1. Parasitic Diseases
(Malaria)
A.Halboup
M.Pharm(Clinical)

2. LEARNING OBJECTIVES
Upon completion of the chapter, the reader will be able to:
1. Describe the presenting signs and symptoms of malaria.
2. List some specific toxicities of mefloquine.
3. Identify the monitoring parameters for quinidine gluconate in severe malaria.
4. Define the major complications of falciparum malaria.
5. Identify the diagnostic strategies of malaria
6. Design treatment plan for complicated and uncomplicated types of malaria
7. Propose treatment plan for pregnant patient with sever and non-sever malaria
8. Consequences of malaria during pregnancy

3. parasites
GI parasites
(giardiasis and
amebiasis)
protozoan infections
(malaria and
trypanosomiasis)
helminthic diseases
(nematodes and
cestodes)
Ectoparasites
(lice and
scabies)

4. MALARIA
• WHO estimates that 228 million cases of malaria occurred worldwide in 2018 (confidence
interval: 206–258 million) and about 405 000 people died from the disease, mostly children
under 5 years of age in sub-Saharan Africa.
❑ The primary reasons for morbidity and death in malaria are :
❖failure to take recommended chemoprophylaxis,
❖inappropriate chemoprophylaxis,
❖delay in seeking medical care or in initiating therapy promptly, and
❖ misdiagnosis
• Evaluation of a patient should include: specific travel history, details of chemoprophylaxis,
and physical findings (eg, splenomegaly).

5. • Malaria is transmitted by the bites of the Anopheles mosquitoes, which introduce into the
bloodstream one of five species of sporozoites of the plasmodia .
Plasmodia
P.
falciparum
P. Ovale P. vivax
P.
malariae
P.knowlesi

6. • Initial symptoms of malaria are nonspecific and may resemble influenza and include chills,
headache, fatigue, muscle pain, rigors, and nausea. The onset of the symptoms is between 1
and 3 weeks following exposure.
• Fever may appear 2 to 3 days after initial symptoms and may follow a pattern and occur
every 2 or 3 days (P. vivax, P. ovale, and P. malariae).
• Fever with P. falciparum can be erratic and may not follow specific patterns.
– Falciparum malaria (or P. knowlesi) must always be regarded as a life-threatening
medical emergency.

7. Pathophysiology
• Within minutes after the bite of the Anopheles mosquito, the sporozoites invade hepatocytes
and begin an asexual phase called schizonts .
• patient may be asymptomatic during this period. After a lapse of 5 and 15 days (depending
on the species), schizonts rupture to release daughter cells (merozoites) into the blood, which
then invade erythrocytes.
– This asexual phase is about 48 hours for P. falciparum, P. vivax, and P. ovale, and 72
hours for P. malariae.

8. • Unlike P. falciparum and P. malariae, which only remain in the liver for about 3 weeks
before invading erythrocytes, P. ovale and P. vivax can remain in the liver for extended
periods in a latent stage (as hypnozoites); this can result in the recurrence of the infection
after weeks or months.
– primaquine for 14 days therapy is necessary to eradicate this stage of the infection .

9. Clinical Presentation and Diagnosis
• Normally, the appearance of a prodrome with headache, anorexia, abdominal pain, fatigue,
fever, chills, and myalgia which coincides with the erythrocytic phase of malaria, occurs
frequently between 10 and 21 days after being exposed.
• This phase causes extensive hemolysis, which results in anemia and splenomegaly.
• The most serious complications are caused by P. falciparum infections. This attributed to
– (a) its ability to produce high parasitism (up to 80%) of red cells of all ages; and
– (b) the propensity to be sequestered in post capillary venules of critical organs such as
brain, liver, heart, lungs, and kidneys. As results, P. falciparum Contributes to severe
ischemia and metabolic derangements.
• P. malariae is implicated in immune-mediated glomerulonephritis and nephrotic syndrome

10. Diagnosis
• Genotyping of malaria parasites (PCR)
– Innovations for detecting malaria include DNA or RNA probes by PCR and monoclonal
antibody testing (not widely available for clinical use.).
• Microscopic test (the “gold standard”):blood smears were stained with 2.5 % Giemsa for
45 min and examined at a magnification of 1000×.
• A P. falciparum–specific monoclonal antibody test, histidine-rich protein 2 (HRP-2), is fairly
sensitive for P. falciparum and is recommended by the World Health Organization as an
alternative for microscopic test.
– rapid malaria diagnostic tests (RDTs) are restricted from wide use by cost, regulatory
standards, operative expertise, and availability.

11. Treatment
• The primary goal in the management of malaria is the rapid identification of the
Plasmodium species by blood smears (both thick and thin smears repeated every 12 hours
for 3 days).
• Antimalarial therapy should be initiated promptly to eradicate the infection within 48 to
72 hours and avoid complications such as hypoglycemia, pulmonary edema, and renal
failure.
• The presence of parasites in the blood 3
to 5 days after initiation of therapy
suggests resistance to the drug regimen.

12. Pharmacologic Therapy
• In an uncomplicated attack of malaria (for all plasmodia except chloroquine-resistant P.
falciparum and P. vivax), the recommended oral regimen is chloroquine 600 mg (base)
initially, followed by 300 mg (base) 6 hours later, and then 300 mg (base) daily for 2 days .?
• In severe illness or falciparum malaria, patients should be admitted to an acute care unit,
and quinidine gluconate 10 mg salt/kg as a loading dose (maximum 600 mg) in 250 mL
normal saline should be administered IV slowly over 1 to 2 hours.
• This should be followed by continuous infusion of 0.02 mg/kg/min of quinidine for at least 24
hours until oral therapy can be started.
– In patients who have received either quinine or mefloquine, the loading dose of
quinidine should be omitted.
• Oral quinine salt (650 mg every 8 hours) plus doxycycline 100 mg twice daily should follow
the IV dose of quinidine to complete 7 days of therapy.

13. Pharmacologic Therapy cont…
• In patients who cannot tolerate quinidine or if quinidine is not readily available,
IV artesunate 2.4 mg/kg/dose for 3 days, at 0, 12, 24, 48, and 72 hours may be used, followed by
oral therapy.
– Oral therapy may include doxycycline, mefloquine , clindamycin, or atovaquone/proguanil,
• Acute P. falciparum malaria resistant to chloroquine should be treated with IV quinidine .
• Hypoglycemia, that is associated with both P. falciparum and quinidine administration,
should be checked every 6 hours and when necessary, corrected with dextrose (5%–10%)
infusions.
– Complication of falciparum malaria include : pulmonary edema, hypoglycemia,
jaundice, renal failure, confusion, delirium, seizures, coma, and death,

14. Pharmacologic Therapy cont…
• Quinidine infusions should be slowed or stopped if
– the QT interval is greater than 0.6 second,
– the increase in the QRS complex is greater than 25%, or
– hypotension unresponsive to fluid challenge results.
• Quinidine levels should be maintained at 3 to 7 mg/dL.
• Monitor (ECG, BP, BS) when Quinidine is used.
• In P. falciparum, P. vivax, P. ovale, or P. malariae (chloroquineresistant) infections, a dose of 750 mg
of mefloquine followed by 500 mg 12 hours later is recommended.
– Mefloquine is associated with sinus bradycardia, confusion, hallucinations, and psychosis and
should be avoided in patients with a history of epilepsy, cardiovascular problems or depression.

15. Pharmacologic Therapy cont…
• In patients who have P. vivax or P. ovale malaria , following the treatment of the acute
phase of malaria and screening for glucose-6-phosphate dehydrogenase(G6PD) deficiency,
patients should receive a regimen of primaquine for 14 days to ensure eradication of the
hypnozoite stage of P. vivax or P. ovale.
• The main adverse effect of primaquine is haemolytic anaemia in individuals with glucose-
6-phosphate dehydrogenasedeficiency (G6PDd).

16. Pregnant Women with malaria
• Pregnant women are three times more likely to develop severe disease than non-pregnant
women.
• Malaria infection during pregnancy can lead to :
– miscarriage, premature delivery, low birth weight, congenital infection, and/or perinatal
death.
• For pregnant women diagnosed with uncomplicated malaria caused by P. malariae, P. vivax,
P. ovale, or chloroquine-sensitive P. falciparum infection, prompt treatment with
chloroquine (treatment schedule as with non-pregnant adult patients) is recommended.
– Alternatively, hydroxychloroquine may be given instead.
• For women in their second or third trimesters, artemether-lumefantrine is an additional
option.

17. • Quinine treatment should continue for 7 days for infections acquired in Southeast Asia
and for 3 days for infections acquired elsewhere; clindamycin treatment should continue
for 7 days regardless of where the infection was acquired. (1st trimester :quinine
+clindamycin for 7 days )
• For pregnant women diagnosed with uncomplicated malaria caused by chloroquine-
resistant P. vivax infection, prompt treatment with artemether-lumefantrine (second and
third trimesters) or mefloquine (all trimesters) is recommended.
• IV artesunate is safe in infants, children, and pregnant women in the second and third
trimesters (used only for severe malaria).

18. Treatment: Severe Malaria
All patients with severe malaria, regardless of infecting species, should be treated with
intravenous (IV) artesunate.
• Oral medications can be used till arriving of IV artesunate
– Artemether/lumefantrine (Coartem®):
– Atovaquone/proguanil (Malarone®):
– Quinine: Adults: 650 mg (salt) every 8 hours.
– When IV artesunate arrives, discontinue the oral medication.
• The dosing of IV artesunate is as follows: Adults and children ≥20 kg: 2.4 mg/kg at 0 hour, 12
hours, and 24 hours; and 48 hours
– IV artesunate is safe in infants, children, and pregnant women in the second and third trimesters.

20. Literature

21. Dose and duration of ttt regimens
• In the AS + SP studies the patients received a dose of 4 mg/kg/day artesunate once a day
for 3 days and a single administration of 25/1.25 mg/kg SP on day 0.
• In studies on AL, the patients were given AL (Coartem®, Novartis) according to body weight
bands.
– Patients weighing 5–14 kg received one tablet (20 mg artemether plus 120 mg lumefantrine)
per dose,
– those weighing 15–24 kg received two ,
– those weighing 25–34 kg three tablets, and
– those weighing ≥35 kg received four tablets.
• In total, six doses were administered at hours 0, 8, 24, 36, 48, and 60

22. Malaria prophylaxis
• Chloroquine: 300 mg base (500 mg salt), once/week.
– Begin 1-2 weeks before travel, once/week during travel, and for 4 weeks after leaving.
• Mefloquine 250 mg weekly
– 1 tablet weekly. Begin 1-2 weeks before travel, weekly during travel, and for 4 weeks
after leaving.
• Doxycycline : 100 mg daily.
– Begin 1-2 days before travel, daily during travel, and for 4 weeks after leaving.
• Primaquine 30 mg base, daily (NOT recommended in (G6PD) deficiency.
– Begin 1-2 days prior to travel, daily during travel, and for 7 days after leaving

23. Summary
• Malaria is transmitted by the bites of the Anopheles mosquitoes(female)
• There are five species of malaria (P. falciparum 99%, P. ovale, P. vivax, P. malariae, and P.knowlesi).
• Falciparum malaria must always be regarded as a life-threatening medical emergency.
• Clinical presentation (headache, anorexia, abdominal pain, fatigue, fever, chills, and myalgia , occur 10-21 day
after exposure)
• Diagnosis : microscopic test, PCR, RDT(hrp-2)
• Treatment : complicated (IV:artesunate 2.4mg/kg/dose for 3days(0,12,24,36,72) or quinidine (loading and
continuous dose ), all ttt showed by followed by oral therapy for 7 days . Oral therapy: doxycycline, mefloquine ,
clindamycin, or atovaquone/proguanil,.
– Monitor (ECG, BP, BS) when Quinidine is used.
• Uncomplicated cases : orally (coartum, chloroquine, hydroxychloroquine, mefloquine, quinine plus doxycycline).
• In patients who have P. vivax or P. ovale malaria , following the treatment of the acute phase, a regimen of
primaquine for 14 days. Why ?
• Sever cases of malaria : artesunate for 3 days (0, 12, 24, 48, 72) followed by ordal therapy for 7 days.
• Malaria in pregnant woman: mefloquine for all semester , artesunate or artemether with lumefantrine for 2nd and
3rd trimester.

24. Case study

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