Overview -
Malaria is an acute febrile illness caused by protozoan parasites of the genus Plasmodium.
It remains one of the world’s most significant public health challenges,
particularly in tropical and subtropical regions. The disease is transmitted to
humans through the bite of an infective female Anopheles mosquito.
1. Causative Agents
There are
five Plasmodium species known to commonly infect humans:
- Plasmodium falciparum – the most lethal and
widespread in sub-Saharan Africa
- Plasmodium vivax – causes relapsing malaria;
prevalent in Asia and Latin America
- Plasmodium ovale – similar to P. vivax
but less common; found in West Africa and the Pacific Islands
- Plasmodium malariae – causes a more chronic
infection; scattered distribution worldwide
- Plasmodium knowlesi – zoonotic malaria from
macaque monkeys; emerging in Southeast Asia
2. Life Cycle & Transmission
- Sporozoite Stage (Mosquito →
Human):
- An infected Anopheles
mosquito injects sporozoites into the human bloodstream during a blood
meal.
- Sporozoites travel to
hepatocytes (liver cells).
- Schizogony in Liver
(Exoerythrocytic Stage):
- In hepatocytes, sporozoites
mature into schizonts, which rupture and release merozoites into the
bloodstream.
- In species like P. vivax
and P. ovale, hypnozoites can remain dormant in the liver for
weeks to months, causing relapses.
- Erythrocytic Cycle (Blood
Stage):
- Merozoites invade red blood
cells (RBCs), develop from ring forms → trophozoites → schizonts →
rupture, releasing more merozoites.
- This cycle (approximately
48–72 hours, depending on species) corresponds to the characteristic
fever spikes.
- Gametocyte Formation (Sexual
Stage):
- Some merozoites
differentiate into sexual forms called gametocytes.
- When a mosquito bites an
infected person, it ingests gametocytes, which mature in the mosquito gut
to form sporozoites.
- Sporozoite Development in
Mosquito:
- Within the mosquito, the
parasite undergoes fertilization → ookinete → oocyst → release of
sporozoites that migrate to the salivary glands—ready to infect the next
human host.
3. Clinical Presentation
A. Incubation Period
- P. falciparum: typically 9–14 days
- P. vivax / P. ovale: around 12–18 days, but
relapses may occur months later
- P. malariae: roughly 18–40 days
B. Common Early Symptoms
- Fever (classically tertian for P.
vivax, P. ovale, P. falciparum, P. knowlesi;
quartan for P. malariae)
- Chills and rigors
- Sweating episodes as fever resolves
- Headache
- Myalgia (muscle aches)
- Malaise and fatigue
C. Gastrointestinal Symptoms
- Nausea and Vomiting – often seen in first
malaria attacks, particularly with high parasitemia (most common in P.
falciparum).
- Diarrhea or watery stools can occur,
especially in children.
D. Respiratory and Other Features
- Cough (nonproductive)
- Shortness of breath (may indicate pulmonary
edema in severe falciparum)
- Abdominal pain (from splenomegaly or
hepatomegaly)
- Anemia (due to hemolysis of
infected and uninfected RBCs)
- Jaundice, especially when
parasitemia is high
E. Severe Malaria
Most
commonly caused by P. falciparum, but P. knowlesi can also lead
to severe disease. Criteria include:
- Cerebral malaria: altered consciousness,
seizures, coma
- Severe anemia: hemoglobin < 5 g/dL or
hematocrit < 15 %
- Acute kidney injury: oliguria/anuria, raised
creatinine
- Acute respiratory distress
syndrome (ARDS)
- Hypoglycemia (often in children or
pregnant women)
- Metabolic acidosis (lactic acidosis)
- Hyperparasitemia (> 5 %–10 % infected
RBCs)
- Shock (circulatory collapse)
4. Diagnosis
- Microscopy (Gold Standard)
- Thick smear: more sensitive for
detecting low parasite densities; used to confirm presence/absence.
- Thin smear: allows species
identification and quantification (parasites per microliter).
- Rapid Diagnostic Tests
(RDTs)
- Detect species-specific
antigens (e.g., histidine-rich protein II [HRP-II] for P. falciparum;
pan-Plasmodium LDH).
- Useful where microscopy is
unavailable.
- Polymerase Chain Reaction
(PCR)
- High sensitivity and
specificity; used for species confirmation, especially with low
parasitemia.
- More costly and
time-consuming; often reserved for reference labs.
- Other Tests
- Complete Blood Count (CBC): reveals anemia;
thrombocytopenia is common.
- Blood chemistries: renal function, liver
enzymes, bilirubin, electrolytes (important for severe cases).
5. Treatment
A. Uncomplicated Malaria
- Plasmodium falciparum (chloroquine-resistant
regions):
- Artemisinin-based
Combination Therapies (ACTs) are first-line (e.g.,
artemether-lumefantrine, artesunate-amodiaquine).
- In areas still sensitive to
chloroquine (now rare): chloroquine (25 mg base/kg over 3 days).
- Plasmodium vivax /
Plasmodium ovale:
- Chloroquine (25 mg base/kg over 3
days), provided no resistance.
- After blood schizonticide
to clear parasitemia, give primaquine (0.25 mg/kg daily for 14
days) to eradicate hypnozoites and prevent relapse.
- Prior to primaquine,
screen for G6PD deficiency to avoid hemolysis.
- Plasmodium malariae:
- Chloroquine is effective (typically
given 25 mg base/kg over 3 days).
- Plasmodium knowlesi:
- Treatment parallels P.
falciparum – ACTs or chloroquine where sensitive; monitor closely due
to risk of rapid parasitemia rise.
B. Severe Malaria (Medical Emergency)
- Intravenous (IV) Artesunate (preferred) or IV
quinidine/quinine if artesunate unavailable.
- Once the patient can
tolerate oral medication and parasitemia has dropped, switch to an ACT.
- Supportive care: manage
hypoglycemia, transfuse for severe anemia, treat acute kidney injury, and
monitor for cerebral complications.
6. Prevention & Control
A. Vector Control
- Insecticide-Treated Nets
(ITNs):
sleeping under long-lasting insecticide-treated bed nets reduces mosquito
bites at night.
- Indoor Residual Spraying
(IRS):
spraying insecticide on interior walls; effective in regions with stable
transmission.
- Larval Source Management: draining or treating
standing water where Anopheles mosquitoes breed.
B. Personal Protective Measures
- Use of Insect Repellents: DEET or picaridin-based
repellents on exposed skin.
- Wearing Protective Clothing: long sleeves and pants,
especially during dawn/dusk when mosquitoes are most active.
C. Chemoprophylaxis (for Travelers)
- Atovaquone–proguanil: begin 1–2 days before
travel, continue daily during stay and 7 days after leaving.
- Doxycycline: start 1–2 days before,
daily during travel, and 4 weeks after departure.
- Mefloquine: weekly dosing beginning 2
weeks before travel, during travel, and 4 weeks after returning (watch for
neuropsychiatric side effects).
- Chloroquine (where sensitive): weekly
dosing starting 1–2 weeks before, weekly during travel, and 4 weeks after
return.
D. Vaccine Developments
- RTS,S/AS01 (Mosquirix™):
- WHO recommended in October
2021 for broad use in children in regions with moderate to high P.
falciparum transmission.
- Provides partial
protection; efficacy wanes over time, booster doses needed.
- R21/Matrix-M:
- Shows promising Phase
II/III results with higher efficacy; licensed in some African pilot
programs (as of mid-2023).
7. Global Burden & Epidemiology
- Estimated Cases (2023): ~247 million cases
worldwide.
- Estimated Deaths (2023): ~608,000 deaths, mostly
children under 5 in sub-Saharan Africa.
- High-Burden Countries: Nigeria, Democratic
Republic of the Congo, Uganda, Mozambique, and Burkina Faso account for
over half of the global malaria burden.
- Seasonality: Transmission often peaks
during or just after rainy seasons when mosquito breeding sites are
plentiful.
- Resistance Patterns:
- Artemisinin resistance has emerged in parts of
Southeast Asia (e.g., Cambodia, Thailand, Myanmar border regions).
- Chloroquine resistance is widespread for P.
falciparum and increasingly reported for P. vivax in certain
areas of Oceania and South America.
8. Special Populations
- Pregnant Women:
- Higher risk of severe
malaria, miscarriage, stillbirth, and low birth weight.
- Intermittent preventive
therapy in pregnancy (IPTp) with sulfadoxine–pyrimethamine is recommended
in endemic areas.
- Infants and Young Children:
- Account for the majority of
malaria mortality; limited immunity leads to rapid progression to severe
disease.
- Immunocompromised Patients
(e.g., HIV Co-infection):
- Higher risk of severe
disease and treatment failures; require close monitoring.
9. Complications & Long-Term Sequelae
- Neurological Impairment: Post-cerebral malaria
survivors (especially children) may develop cognitive deficits, motor
abnormalities, or behavioral issues.
- Anemia & Splenomegaly: Chronic or repeated
infections can cause splenic enlargement and chronic hemolytic anemia.
- Renal Failure: Blackwater fever
(intravascular hemolysis) can lead to acute tubular necrosis.
- Respiratory Distress: Pulmonary edema may occur
in severe P. falciparum.
10. Summary of Key Points
- Malaria is caused by Plasmodium
parasites transmitted by infected Anopheles mosquitoes.
- Classic symptoms include
cyclical fevers, chills, headache, myalgia, and gastrointestinal
complaints such as nausea and vomiting.
- Diagnosis relies primarily
on microscopy, with RDTs and PCR serving as adjuncts.
- Treatment varies by species
and severity; ACTs are first-line for uncomplicated P. falciparum,
while chloroquine + primaquine is used for P. vivax/ovale.
- Preventive strategies—ITNs,
IRS, chemoprophylaxis, and (where available) vaccination—are critical to
reduce morbidity and mortality.
- Global control efforts focus
on reducing transmission, managing drug resistance, and expanding vaccine
coverage.
Common Symptom Highlights
- Nausea and Vomiting: Frequently reported,
especially in high-parasitemia P. falciparum cases; can precede the
onset of fever.
- Diarrhea: Occurs in a subset of
patients (more often children), may be mild to moderate.
By
understanding the parasite life cycle, clinical features, diagnostic tools, and
treatment/prevention modalities, healthcare providers can both manage
individual cases and contribute to broader malaria control initiatives.
