Malaria

Overview

Malaria is a febrile illness caused by protozoa of the genus Plasmodium, transmitted by the bite of an infected female Anopheles mosquito. It remains common in Pakistan, especially in Sindh, Balochistan and areas affected by floods, with cases peaking after the monsoon.

P. vivax causes most cases in Pakistan; P. falciparum causes a smaller share but almost all severe malaria and deaths. Any fever in someone living in, or returning from, a malarious area is malaria until proved otherwise.

Species

Life cycle

1. The mosquito injects sporozoites from its salivary glands.
2. Sporozoites reach the liver within minutes and multiply in hepatocytes (pre-erythrocytic / exo-erythrocytic schizogony). There are no symptoms in this stage.
3. The liver schizont bursts and releases merozoites into the blood.
4. In P. vivax and P. ovale, some sporozoites stay dormant in the liver as hypnozoites, which wake up weeks to months later and cause relapse.
5. Merozoites invade red cells: ring form → trophozoite → schizont; the cell bursts and releases new merozoites (erythrocytic schizogony). Each burst causes a fever paroxysm.
6. Some parasites become gametocytes, which are taken up by a feeding mosquito; sexual reproduction occurs in the mosquito (sporogony).

• Man is the intermediate host; the mosquito is the definitive host (sexual cycle).
• Malaria can also spread by blood transfusion, shared needles and across the placenta. Transfusion malaria has no liver stage, so no relapse.

Pathophysiology

• Fever and rigors: release of parasite products and cytokines (TNF) when schizonts rupture; synchronised bursting gives the tertian (every 48 h) or quartan (every 72 h) pattern.
• Anaemia: haemolysis of infected and uninfected cells, splenic removal, marrow suppression (dyserythropoiesis), folate loss.
• Sequestration (falciparum only): infected red cells grow knobs carrying PfEMP1, which stick to endothelium (cytoadherence) and to uninfected cells (rosetting). They block small vessels in the brain, kidney, gut and placenta. The peripheral parasite count can therefore underestimate the total load.
• Protection: sickle cell trait, thalassaemia trait and G6PD deficiency give partial protection against severe falciparum malaria.

Clinical features

• Incubation: usually about 10–21 days (falciparum shorter; vivax can present months later).
• Fever with rigors (cold stage), then hot stage, then drenching sweats; well between attacks once the cycle settles.
• Headache, myalgia, vomiting, diarrhoea; splenomegaly, mild jaundice, anaemia.
• Thrombocytopenia is common.

Severe falciparum malaria

Any of these in a patient with falciparum parasites:

Other complications

• Tropical splenomegaly syndrome (hyper-reactive malarial splenomegaly): massive spleen, high IgM, few parasites; responds to long-term antimalarials.
• Burkitt lymphoma: linked with EBV and holoendemic malaria.
• Pregnancy: severe anaemia, hypoglycaemia, placental sequestration, miscarriage, low birth weight; first pregnancies most affected.
• P. malariae nephropathy (immune-complex nephrotic syndrome).

Investigations

• If the first film is negative but suspicion remains, repeat films (at least three, 12–24 hours apart) before excluding malaria.
• Serology has no role in acute diagnosis.
• Falciparum film: multiple fine rings, double chromatin dots, banana-shaped gametocytes; usually only rings and gametocytes seen in peripheral blood.

Differential diagnosis

• Dengue (retro-orbital pain, low platelets, NS1 positive)
• Enteric fever (gradual fever, relative bradycardia, blood culture)
• Leptospirosis, CCHF, viral hepatitis
• Bacterial sepsis and meningitis (lumbar puncture if in doubt; parasites may be incidental in endemic areas)

Management

Uncomplicated P. vivax, P. ovale, P. malariae

• Chloroquine over 3 days (adult: 600 mg base, then 300 mg at 6, 24 and 48 hours), or an ACT where chloroquine resistance or mixed infection is possible.
• Radical cure (vivax, ovale): primaquine 0.25–0.5 mg/kg daily for 14 days to kill hypnozoites.
• Test for G6PD deficiency first: primaquine can cause acute haemolysis, dark urine and anaemia (bite cells and Heinz bodies on the film).
• Primaquine is contraindicated in pregnancy (the fetus's G6PD status is unknown) and in breastfeeding of a G6PD-unknown infant. Give weekly chloroquine to prevent relapse until delivery, then primaquine.

Uncomplicated P. falciparum

• Artemisinin-based combination therapy (ACT) for 3 days, for example artemether–lumefantrine. Others: artesunate–amodiaquine, dihydroartemisinin–piperaquine, artesunate–mefloquine, artesunate–SP.
• Never give an artemisinin alone: the short-acting artemisinin clears most parasites fast, and the long-acting partner drug kills the rest. Monotherapy breeds resistance.
• A single low dose of primaquine acts as a gametocytocide to reduce onward transmission (in low-transmission areas).
• First trimester: WHO now recommends artemether–lumefantrine (older advice was quinine plus clindamycin).

Severe malaria (medical emergency)

• IV artesunate 2.4 mg/kg at 0, 12 and 24 hours, then daily, for at least 24 hours and until the patient can take oral drugs; then complete a full 3-day ACT course.
• Quinine IV (loading dose 20 mg/kg) if artesunate is not available; watch for hypoglycaemia, QT prolongation and cinchonism (tinnitus, deafness, vertigo).
• IM artesunate or rectal artesunate (children) as pre-referral treatment.
• IV artesunate is also used in all trimesters of pregnancy for severe malaria.
• Supportive care: check and correct glucose, careful fluids (avoid overload), transfuse for severe anaemia, dialysis for AKI, anticonvulsants for seizures, antibiotics if bacteraemia suspected.
• Steroids are not given in cerebral malaria (harmful).
• Delayed haemolysis may occur 1–3 weeks after IV artesunate in patients with high parasitaemia; check haemoglobin at follow-up.

Drug mechanisms and side-effects

Prevention

• Long-lasting insecticide-treated nets, indoor residual spraying, removing breeding sites.
• Chemoprophylaxis for travellers: atovaquone–proguanil, doxycycline or mefloquine depending on resistance and patient factors.
• Malaria vaccines (RTS,S and R21) are now used for children in high-burden African settings.

Pakistan note: the national malaria programme sets first-line drugs for vivax and falciparum. These change with resistance patterns, so check the current national guideline.

Quick revision

• Female Anopheles; sporozoite injected; liver then blood.
• Vivax and ovale: hypnozoites → relapse → primaquine 14 days after G6PD check.
• Falciparum: sequestration, cerebral malaria, deaths.
• Malariae: 72-hour fever, nephrotic syndrome.
• Thick film detects; thin film identifies species and counts.
• Uncomplicated falciparum: 3-day ACT.
• Severe: IV artesunate, then oral ACT; glucose checks.
• No primaquine in pregnancy; weekly chloroquine until delivery.

Written by The House Job from standard references (Kumar and Clark's Clinical Medicine; Park's Textbook of Preventive and Social Medicine; Levinson's Review of Medical Microbiology and Immunology).

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