Classify antimalarial drugs by stage of action. Describe chloroquine, the artemisinins and the other agents.

Classification BY Stage of the Parasite

Chloroquine

• Mechanism — concentrates several thousandfold in the parasite food vacuole, where it prevents polymerisation of toxic haem into inert haemozoin; free haem then kills the parasite
• Very large volume of distribution (about 13,000 L) and a long half-life, so a loading dose is needed and the drug persists for weeks
• Uses — P. Vivax malaria (still largely sensitive in India), extraintestinal amoebiasis, rheumatoid arthritis and SLE (as hydroxychloroquine), and photosensitive skin disease
• Adverse effects — nausea, headache, pruritus (troublesome in dark-skinned people and a common cause of non-adherence), blurred vision; with prolonged high-dose use, irreversible retinopathy (bull’s-eye maculopathy), myopathy and ototoxicity; QT prolongation; and it is dangerous IN overdose, causing hypotension and fatal arrhythmia
• Resistance in P. Falciparum is widespread, mediated by the PfCRT transporter which pumps the drug out of the food vacuole; chloroquine is therefore no longer used for falciparum malaria

Artemisinins and Combination Therapy

• Artesunate, artemether, arteether, dihydroartemisinin — derived from Artemisia annua
• Mechanism — the endoperoxide bridge is cleaved by haem iron within the parasite, generating free radicals that alkylate parasite proteins — again, selectivity comes from activation inside the organism
• The fastest-acting antimalarials, clearing parasitaemia more rapidly than any other class, and active against gametocytes so they reduce transmission
• Very short half-life (1–3 hours), so used alone they require long courses and select resistance — hence they are always given as artemisinin-based combination therapy (act) with a longer-acting partner drug that eliminates the residual parasites
• Regimens used in India — artesunate + sulfadoxine-pyrimethamine for falciparum in most of the country, and artemether + lumefantrine in the north-eastern states where sulfadoxine-pyrimethamine resistance is established
• Intravenous artesunate is the treatment of choice for severe malaria, having replaced quinine after large trials showed a clear mortality benefit
• Adverse effects — generally well tolerated; delayed haemolysis some weeks after intravenous artesunate is recognised and requires follow-up haemoglobin checks

Other Antimalarials

Management of Severe Malaria

• Defining features — impaired consciousness or convulsions (cerebral malaria), respiratory distress and acidosis, hypoglycaemia, severe anaemia, renal failure, jaundice, shock, bleeding, and hyperparasitaemia
• Intravenous artesunate is the drug of choice at 0, 12 and 24 hours then daily, followed by a full oral act course once the patient can swallow; this replaced quinine after trials showed a substantial reduction in mortality in both adults and children
• Quinine is the alternative where artesunate is unavailable, given by slow infusion with cardiac monitoring; never as a bolus
• Supportive care determines much of the outcome — monitor and correct hypoglycaemia (which quinine itself causes), avoid fluid overload, transfuse for severe anaemia, dialyse for renal failure, and treat convulsions
• Do not give corticosteroids in cerebral malaria; trials showed prolonged coma and more complications
• Exclude coexisting bacterial sepsis, which is common and easily missed behind a positive malaria test

Applied Aspects

• Test for G6PD deficiency before primaquine wherever possible; where testing is unavailable, a weekly higher-dose regimen for 8 weeks is an alternative in mild deficiency
• Confirm the species before treating — vivax needs radical cure, falciparum needs an act; rapid diagnostic tests and microscopy both have a place
• Severe malaria is a medical emergency — intravenous artesunate, attention to hypoglycaemia, fluid balance, acidosis and anaemia; treat before confirmation if the suspicion is strong
• Never treat falciparum malaria with a single drug, and never use chloroquine for it in India
• Artemisinin resistance has emerged in South-East Asia and is the principal threat to malaria control; protecting these drugs by using proper combinations and avoiding monotherapy is essential
• Prevention outranks treatment — insecticide-treated nets, indoor residual spraying and larval control; India’s malaria burden has fallen substantially with these measures
• Malaria in pregnancy is more severe and causes low birth weight and fetal loss; chloroquine is safe for vivax, and ACTs are used in the second and third trimesters
• Quinine causes hypoglycaemia by stimulating insulin release, and the resulting confusion is easily attributed to cerebral malaria; glucose must be checked repeatedly
• Counterfeit and substandard antimalarials are a real problem in endemic regions, causing treatment failure and driving resistance; sourcing matters
• Take a travel history in any fever, since imported falciparum malaria can kill within days and is missed when the possibility is not considered
• A negative rapid test does not exclude malaria in a strongly suspected case; repeat smears over 24 to 48 hours, since parasitaemia fluctuates
• Vivax malaria causes substantial illness though it rarely kills, and relapses drive much of the burden in India — which is why radical cure matters at a population level, not just for the individual
• Explain the 14-day primaquine course carefully; patients feel well after 2 days and stop, which is why relapse remains common despite correct prescribing
• Mixed infections occur, and a patient treated for falciparum may relapse with vivax months later if radical cure was not given
• Antimalarials are not analgesics for fever — presumptive treatment of every fever without confirmation delays other diagnoses, including dengue, typhoid and scrub typhus, which are all common in India
• Chloroquine is dangerous in overdose and freely available in endemic areas, and is a recognised agent of deliberate self-poisoning; storage matters
• Follow up after treatment to confirm parasite clearance and detect anaemia, particularly after intravenous artesunate
• Report treatment failures, since they are the early signal of emerging resistance and are otherwise invisible to surveillance