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Malaria

Malaria is an acute febrile infection caused by Plasmodium parasites and transmitted mainly through the bite of infected female Anopheles mosquitoes. The most important human species are Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi

Also called

Plasmodium infection

ICD-10

B54

Specialty

Infectious

Onset

Acute

Reviewed

August 2026
On This Page

Overview

–Malaria begins when infected mosquitoes inject Plasmodium sporozoites into the bloodstream. The parasites first multiply in the liver and then infect red blood cells.

 

Important species include:

  • P. falciparum: most likely to cause severe and fatal disease
  • P. vivax: can relapse because of dormant liver hypnozoites
  • P. ovale: can also cause relapse
  • P. malariae: may produce chronic low-grade infection
  • P. knowlesi: can cause rapidly progressive severe disease

Etiology & Risk Factors

-Etiology

–Malaria is caused by intracellular protozoa of the genus Plasmodium. Transmission occurs mainly through infected female Anopheles mosquitoes.

 

Rare transmission can occur through:

  • Blood transfusion
  • Shared needles
  • Congenital transmission

 

-Risk Factors

  • Residence or travel in an endemic area
  • Lack of effective malaria prevention
  • Lack of immunity
  • Young age
  • Pregnancy
  • Immunosuppression

Pathophysiology

Mosquito bite → sporozoites enter blood → hepatic replication → merozoites released → red blood cell invasion → erythrocyte rupture → inflammatory response and fever → repeated cycles of parasitemia → anemia and systemic complications

In P. falciparum infection, infected erythrocytes can adhere to vascular endothelium, causing microvascular obstruction and severe organ dysfunction.

Clinical Presentation

-Symptoms:

Malaria commonly causes:

  • Fever
  • Chills or rigors
  • Headache
  • Sweating
  • Myalgia
  • Fatigue
  • Nausea
  • Vomiting
  • Abdominal discomfort

The fever may be intermittent, but a regular periodic pattern is not always present.

-Signs:

  • Fever

  • Pallor

  • Tachycardia

  • Splenomegaly

  • Hepatomegaly in some patients

  • Jaundice in severe disease

-Severe Disease may cause:

    • Altered consciousness

    • Seizures

    • Severe anemia

    • Hypoglycemia

    • Acute Kidney Injury (AKI)

    • Metabolic acidosis

    • Respiratory distress

    • Hemoglobinuria

    • Shock

    • Multiorgan failure

  •  
Malaria Overview
Malaria Overview

Causative Agents

Malaria · Causative Agents — Plasmodium Species

P. falciparum
Most dangerous
Irregular / continuous
Cerebral malaria · multi-organ failure
P. vivax
Most widespread
48h — Tertian
Relapses · hypnozoites in liver
P. ovale
Mildest
48h — Tertian
Relapses · West Africa
P. malariae
Chronic / quartan
72h — Quartan
Nephrotic syndrome · recrudescence
P. knowlesi
Zoonotic — SE Asia
24h — Quotidian
Rapid deterioration · misidentified as malariae
Species Comparison — All 5 Plasmodium
Feature P. falciparum P. vivax P. ovale P. malariae P. knowlesi
Fever cycle Irregular / continuous — no classic periodicity early 48h — Tertian fever every 3rd day 48h — Tertian fever every 3rd day 72h — Quartan fever every 4th day 24h — Quotidian daily fever
RBC preference All ages — any RBC → highest parasitaemia Young / reticulocytes — Duffy antigen required Reticulocytes — similar to vivax Old RBCs — low parasitaemia All ages — similar to falciparum
RBC changes No enlargement. Knobs on surface — cytoadherence → sequestration in capillaries Enlarged. Schüffner's dots (stippling) Enlarged + oval / fimbriated. Schüffner's dots Not enlarged. Band form trophozoites — diagnostic Not enlarged. Similar to malariae on film — misidentification common
Liver stage No dormant stage — no hypnozoites Hypnozoites — dormant in liver; cause relapses months–years later Hypnozoites — same as vivax; relapses No hypnozoites. Recrudescence — persistent low-level blood infection No hypnozoites. No relapses.
Severity Most severe — cerebral malaria, ARDS, AKI, severe anaemia, hypoglycaemia, DIC Moderate — severe anaemia, splenic rupture possible. Rare cerebral vivax. Mildest — self-limiting. Rarely severe. Mild acutely. Nephrotic syndrome — quartan malaria nephropathy (chronic) Underestimated — rapidly progressive; multi-organ failure possible
Geographic distribution Sub-Saharan Africa (highest burden), South/SE Asia, Americas Worldwide — widest distribution. South/SE Asia, Americas, Africa (limited) West/Central Africa mainly. SE Asia rarely. Sub-Saharan Africa, South/SE Asia, Pacific SE Asia only — Borneo (Malaysia, Indonesia), Philippines. Zoonosis from macaques.
Key morphology Multiple rings per RBC. Accole / appliqué forms. Banana-shaped gametocytes. Large ameboid trophozoites. Schüffner's dots. Merozoites 12–24. Oval/fimbriated RBCs. Schüffner's dots. 8 merozoites. Band form trophozoites — pathognomonic. Rosette schizonts (8 merozoites). Resembles malariae — only PCR/sequencing reliably distinguishes.
Treatment note ACT — artemisinin-based. IV artesunate for severe. Check CQ resistance (almost universal). CQ if sensitive + Primaquine — eliminates hypnozoites. Check G6PD first. CQ + Primaquine — same as vivax for hypnozoites. Shorter course. CQ — usually sensitive. No primaquine needed (no hypnozoites). ACT or CQ (usually sensitive). Treat promptly — rapid deterioration.
Primaquine rule: Only needed for P. vivax and P. ovale — to eradicate liver hypnozoites and prevent relapse. Always check G6PD before giving primaquine — causes haemolytic anaemia in G6PD-deficient patients. Tafenoquine — newer alternative; single dose; also requires G6PD check.
Vector & Life Cycle — Key Points
Vector
Female Anopheles mosquito — only female feeds on blood (needs protein for eggs)
Bites at dusk and dawn — peak transmission night
P. knowlesi — also transmitted by Anopheles leucosphyrus group; reservoir = macaque monkeys
Non-vector transmission: blood transfusion, shared needles, congenital (mother → fetus), organ transplant
Human (asexual) cycle
Sporozoites injected → travel to liver
Liver stage (exo-erythrocytic) — sporozoites → hepatocytes → schizonts → merozoites (vivax/ovale → hypnozoites too)
Blood stage (erythrocytic) — merozoites invade RBCs → ring → trophozoite → schizont → rupture → fever spike
Fever = RBC rupture releasing merozoites + toxins (haemozoin)
Some → gametocytes (sexual stage) — taken up by mosquito
Mosquito (sexual) cycle
Mosquito ingests gametocytes during blood meal
Gametocytes → zygote → ookinete → oocyst in stomach wall
Oocyst matures → ruptures → sporozoites migrate to salivary glands
Sporozoites injected into next human host during bite
Falciparum gametocytes — banana-shaped, appear 10 days after infection (latest)
High-Yield Exam Facts
Unique features per species
P. falciparum — only species causing cerebral malaria. Banana gametocytes. No relapse. Multiple rings per cell. Appliqué form.
P. vivax — requires Duffy antigen (West Africans Duffy-negative = naturally resistant). Widest global distribution. Schüffner's dots.
P. ovale — oval + fimbriated RBCs. Mildest. Can relapse like vivax but less frequently.
P. malariae — band form trophozoites + rosette schizonts. Quartan (72h) fever. Quartan nephropathy — nephrotic syndrome in children.
P. knowlesi — quotidian (24h) fever. Zoonosis — macaques. SE Asia only. Misidentified as malariae on film — PCR needed.
Protective factors + associations
Sickle cell trait (HbAS) — protective against severe falciparum malaria. Parasite growth impaired in sickle cells.
G6PD deficiency — some protection against malaria. Oxidative stress kills parasite. BUT primaquine causes haemolysis — always screen.
Duffy negativity — West Africans resistant to P. vivax (no receptor on RBC).
HbC, HbE, alpha/beta thalassaemia — partial protection against falciparum.
Burkitt's lymphoma — EBV + chronic falciparum malaria (Africa). Malaria drives EBV-infected B-cell proliferation.
Tropical splenomegaly syndrome — hyperreactive malarial splenomegaly; chronic P. vivax/falciparum; massive spleen + high IgM.
Fever periodicity hook: FalciParum = irregular/continuous (Falci = Flexible). Vivax/ovale = 48h tertian (every 3rd day). Malariae = 72h quartan (every 4th day). Knowlesi = 24h quotidian (daily — Know = Now = daily). Hypnozoites (relapse) = Vivax + Ovale only — both need Primaquine. Recrudescence (not relapse) = Malariae.

History Taking

-Ask about:

  • Fever and duration
  • Chills and rigors
  • Recent travel or residence in a malaria-endemic region
  • Previous malaria infection
  • Use of mosquito protection
  • Malaria chemoprophylaxis
  • Pregnancy
  • Antimalarial treatment already received
  • Blood transfusion or injection exposure

Physical Examination

-General Examination

  • Temperature
  • Blood pressure
  • Heart rate
  • Respiratory rate
  • Mental status
  • Hydration
  • Pallor
  • Jaundice

 

-System-Specific Examination:

  • Splenomegaly
  • Hepatomegaly
  • Neurological examination
  • Respiratory assessment
  • Assessment for signs of shock

Investigations

-Complete Blood Count

Important for detecting:

  • Anemia

  • Thrombocytopenia

  • Leukocyte abnormalities

 

-Peripheral Blood Film

Essential for diagnosis.

Thick and thin blood films can:

  • Detect parasites

  • Identify Plasmodium species

  • Estimate parasite density

 

-Biochemistry / Specific Tests

  • Blood glucose

  • Serum electrolytes

  • Urea and creatinine

  • Liver function tests

  • Lactate and blood gas analysis in severe disease

 

Rapid Diagnostic Tests

Malaria antigen rapid diagnostic tests can provide rapid evidence of infection but may not reliably determine parasite density or distinguish every species.

 

-Imaging

Not routinely required.

Imaging is directed toward complications or alternative diagnoses.

 

-Special / Confirmatory Tests

Repeat blood films may be necessary when initial testing is negative but clinical suspicion remains high.

Parasitemia should be quantified in confirmed infection, particularly when severe falciparum disease is suspected.

Diagnosis

-Diagnosis is Established by detecting Plasmodium parasites or parasite antigens in the blood.

Fever + compatible exposure → blood film and/or rapid diagnostic test → identify species and parasite density → assess for severe disease

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Management

Malaria · Severe Malaria — Criteria & Management

WHO Criteria for Severe Malaria (P. falciparum)
Neurological
Cerebral malaria — unarousable coma, GCS ≤2 (Blantyre) or ≤9 (adult)
Seizures — >2 in 24h
Prostration — inability to sit/stand
Haematological / metabolic
Severe anaemia — Hb <7 g/dL (adults) or <5 g/dL (children)
Hypoglycaemia — glucose <2.2 mmol/L
Hyperparasitaemia — >5% RBCs parasitised (falciparum)
Metabolic acidosis — pH <7.25 or bicarbonate <15
Organ failure
Acute kidney injury — creatinine >265 μmol/L
ARDS / pulmonary oedema — respiratory distress
Circulatory collapse / shock — "algid malaria"
Abnormal bleeding / DIC
Haemoglobinuria — "blackwater fever"
Severe Malaria — Treatment
Drug / InterventionDose & RouteRoleNotes
IV Artesunate
1st line — gold standard		 2.4 mg/kg IV at 0, 12, 24h → then daily until able to take oral Fastest parasite clearance of any antimalarial. Reduces mortality vs quinine by 35%. Crosses blood-brain barrier. Safe in pregnancy. Switch to oral ACT × 3 days to complete course once conscious. Monitor for post-artesunate delayed haemolysis (PADH) — day 7–30.
IV Quinine
Alternative if artesunate unavailable		 Loading dose: 20 mg/kg IV over 4h. Maintenance: 10 mg/kg q8h. Switch to oral when possible. Effective but inferior to artesunate. Use with Doxycycline or Clindamycin (adds antibacterial + antimalarial synergy). Monitor ECG — QT prolongation, arrhythmia. Hypoglycaemia — stimulates insulin. Cinchonism: tinnitus, hearing loss, dizziness.
IM Artemether
If IV access unavailable		 3.2 mg/kg IM loading → 1.6 mg/kg IM daily Alternative to IV artesunate when IV access not possible. Less reliable absorption than IV. Preferably switch to IV artesunate / oral ACT as soon as possible.
Rectal Artesunate
Pre-referral — community level		 10 mg/kg PR single dose WHO-recommended pre-referral treatment for children <6 years with severe malaria when IV not available. Buys time for transfer. Refer immediately after giving. Not a substitute for definitive IV treatment.
IV Artesunate vs IV Quinine: AQUAMAT trial (Africa) and SEAQUAMAT trial (Asia) both showed IV artesunate reduces mortality by ~35% vs quinine. Artesunate is now WHO 1st line for severe malaria worldwide. Quinine only if artesunate unavailable.

Malaria · Treatment by Species

Uncomplicated Malaria — Species-Specific Treatment
Species1st LineAlternativeSpecial considerations
P. falciparum
Most dangerous		 ACT — Artemether-Lumefantrine (Coartem) — 6 doses over 3 days. Take with fatty food (↑ lumefantrine absorption).
Or Artesunate-Amodiaquine / Artesunate-Mefloquine — region-dependent		 Atovaquone-Proguanil (Malarone) — 3 days. Good for travel. No G6PD issue.
Quinine + Doxycycline × 7 days — if ACT unavailable		 Chloroquine resistance near-universal — never use alone for falciparum. Pregnant 1st trimester: Quinine + Clindamycin (avoid ACT). 2nd/3rd trimester: ACT safe.
P. vivax
Relapse risk		 Chloroquine 25 mg/kg over 3 days (where sensitive)
+ Primaquine 15 mg OD × 14 days — eliminates hypnozoites
OR Tafenoquine single dose — newer alternative		 CQ-resistant vivax (Papua New Guinea, Indonesia, parts of SE Asia): ACT + Primaquine Check G6PD before primaquine/tafenoquine — haemolytic anaemia in G6PD deficiency. Tafenoquine: contraindicated if G6PD <70%. Pregnancy: CQ only — no primaquine.
P. ovale
Mildest		 Chloroquine + Primaquine 15 mg OD × 14 days
(Same as vivax — also has hypnozoites)		 ACT — if CQ resistant (rare for ovale) Check G6PD before primaquine. Shorter course than vivax sometimes used (30 mg × 7 days in non-G6PD deficient).
P. malariae
Quartan		 Chloroquine 25 mg/kg over 3 days — universally sensitive ACT — if uncertain species No primaquine needed — no hypnozoites. Monitor renal function — quartan nephropathy. Recrudescence possible (not relapse).
P. knowlesi
Zoonotic		 Chloroquine — usually sensitive
ACT — if severe or uncertain		 Artemether-Lumefantrine Treat promptly — can deteriorate rapidly despite mild initial presentation. No hypnozoites. No primaquine.
ACT = Artemisinin Combination Therapy — artemisinin derivative (rapid action, short half-life) + partner drug (longer half-life, clears residual parasites). Never use artemisinin alone — resistance risk. Check local resistance patterns — partner drug varies by region.

Complications

  • Severe anemia
  • Cerebral malaria
  • Hypoglycemia
  • Acute Kidney Injury (AKI)
  • Metabolic acidosis
  • Respiratory distress
  • Hemoglobinuria
  • Jaundice
  • Shock
  • Multiorgan failure
  • Death

Prognosis

The prognosis depends on the species, parasite burden, age, pregnancy status, immune status, and speed of treatment. Uncomplicated disease usually responds well to appropriate therapy. Severe P. falciparum or P. knowlesi infection can progress rapidly and may be fatal without prompt treatment.

Key Points / Clinical Pearls

  • Malaria is caused by Plasmodium parasites.
  • It is transmitted mainly by infected female Anopheles mosquitoes.
  • P. falciparum is the species most associated with severe disease.
  • P. vivax and P. ovale can relapse from dormant liver stages.
  • Fever, chills, headache, and malaise are common.
  • A regular periodic fever pattern is not required.
  • Recent travel or residence in an endemic area is a major diagnostic clue.
  • Thick and thin blood films are central to diagnosis.
  • Rapid diagnostic tests can provide rapid evidence of infection.
  • Parasite density should be assessed in confirmed disease.
  • Severe Disease can cause cerebral disease, severe anemia, hypoglycemia, and kidney injury.
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  • Milner DA Jr. Malaria Pathogenesis. Cold Spring Harb Perspect Med. 2018;8(1):a025569. PubMed .
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