Discuss malaria — treatment, drug classes, contraindications, side effects, efficacy and prophylaxis

Malaria is caused by five species of Plasmodium — P. falciparum (severe disease and death), P. vivax (relapsing, dominant in India), P. ovale, P. malariae and P. knowlesi (zoonotic, South-East Asia) — transmitted by the female Anopheles mosquito.

Global burden: the World Malaria Report 2025 estimates 282 million cases and 610,000 deaths in 2024, an increase of about 9 million cases on the previous year, driven by drug and insecticide resistance, climate change, conflict and funding contraction.

India: cases have fallen from around 7.5 crore at Independence to about 2.5 lakh confirmed cases and 86 deaths in 2024 — a fall of more than 97%. India exited the WHO ‘High Burden to High Impact’ group in 2024 and targets zero indigenous cases by 2027 and certification of elimination by 2030. In 2024 India still accounted for about 73% of the WHO South-East Asia Region's estimated cases.

Why malaria matters in the geriatric patient: loss of acquired immunity in previously endemic areas, blunted fever, presentation as delirium, falls or unexplained deterioration rather than classical paroxysms, a higher risk of severe disease with renal failure, ARDS, hypoglycaemia and cerebral malaria, and greater vulnerability to antimalarial toxicity through polypharmacy, QT prolongation and impaired renal and hepatic clearance.

Quinoline blood schizonticides: chloroquine, amodiaquine, quinine, mefloquine, lumefantrine, piperaquine, pyronaridine — act by inhibiting haem detoxification in the parasite food vacuole.

8-Aminoquinolines (tissue schizonticides/hypnozoiticides and gametocytocides): primaquine and tafenoquine — the only drugs that achieve radical cure by eradicating P. vivax and P. ovale hypnozoites; both cause haemolysis in G6PD deficiency.

Artemisinins: artesunate, artemether, dihydroartemisinin, arteether — endoperoxide bridge generates free radicals on contact with haem iron. They are the most rapidly acting antimalarials, killing ring stages and reducing parasite biomass 10,000-fold per cycle, but have a very short half-life, hence the mandatory combination with a longer-acting partner drug.

Antifolates: sulfadoxine–pyrimethamine (sequential blockade of dihydropteroate synthase and dihydrofolate reductase), proguanil. Antibiotic antimalarials: doxycycline, clindamycin (apicoplast inhibitors, slow-acting, always used as partners). Naphthoquinone: atovaquone (cytochrome bc1 inhibitor), used with proguanil.

Uncomplicated P. falciparum malaria is treated with an artemisinin-based combination therapy (ACT) for 3 days — the artemisinin clears the parasite biomass and the partner drug eliminates the residuum. WHO recommends six ACTs: artemether–lumefantrine, artesunate–amodiaquine, artesunate–mefloquine, artesunate–sulfadoxine–pyrimethamine, dihydroartemisinin–piperaquine and artesunate–pyronaridine.

India's National Drug Policy on Malaria uses AS+SP (artesunate 3 days + sulfadoxine–pyrimethamine on day 1) as first-line for P. falciparum across most of the country, plus primaquine 0.75 mg/kg single dose on day 2 as a gametocytocide. In the north-eastern states, where SP resistance is established, first-line is artemether–lumefantrine.

P. vivax: chloroquine 25 mg base/kg over 3 days (10–10–5 mg/kg) for the blood stage, plus primaquine 0.25 mg/kg daily for 14 days for radical cure in India (WHO now advises a higher total dose — 7 mg/kg, given as 0.5 mg/kg/day for 14 days or 1 mg/kg/day for 7 days). Where chloroquine resistance exists, an ACT is used instead.

Severe malaria — the single most important therapeutic point: intravenous artesunate is the drug of choice in all patients, including the elderly, pregnant women in all trimesters and children, at 2.4 mg/kg at 0, 12 and 24 hours and then daily. It reduced mortality by 35% compared with quinine in SEAQUAMAT and by 22.5% in AQUAMAT. Give at least 24 hours of parenteral therapy, then complete with a full oral ACT course once the patient can swallow.

Supportive management of severe malaria: hourly glucose monitoring (hypoglycaemia is common, and quinine worsens it by stimulating insulin release), cautious fluid resuscitation with careful attention to pulmonary oedema in the elderly, renal replacement therapy for acute kidney injury or blackwater fever, treatment of seizures, exclusion of concomitant bacterial sepsis, and avoidance of routine exchange transfusion, corticosteroids and heparin, none of which improve outcome.

Reducing transmissibility: in low-transmission areas a single low dose of primaquine 0.25 mg/kg should be given with an ACT to patients with P. falciparum malaria to kill gametocytes; G6PD testing is not required at this dose.

Primaquine and tafenoquine are contraindicated in G6PD deficiency (haemolysis), in pregnancy, in infants under 6 months and in women breastfeeding infants under 6 months. G6PD status must guide radical-cure prescribing; where testing is unavailable, weekly primaquine 0.75 mg/kg for 8 weeks under supervision is the compromise regimen.

Key adverse effects by drug: chloroquine — pruritus (especially in dark skin), retinopathy on prolonged use, myopathy and worsening of myasthenia gravis, QT prolongation; quinine — cinchonism (tinnitus, deafness, headache, nausea, visual disturbance), hypoglycaemia, hypotension on rapid infusion, QT prolongation; mefloquine — neuropsychiatric reactions, contraindicated in epilepsy and psychiatric illness; sulfadoxine–pyrimethamine — Stevens–Johnson syndrome, agranulocytosis, sulfa allergy; doxycycline — photosensitivity, oesophagitis (a real hazard in the older patient — take upright with water), contraindicated in pregnancy; artemisinins — generally very well tolerated, with a recognised post-artesunate delayed haemolysis at 1–3 weeks requiring follow-up haemoglobin; piperaquine and halofantrine — marked QT prolongation.

Geriatric prescribing cautions: the cumulative QT burden of chloroquine, quinine, mefloquine, piperaquine and lumefantrine on top of existing antipsychotics, antiemetics, macrolides and antiarrhythmics; dose adjustment of quinine in renal and hepatic impairment; risk of hypoglycaemia in the diabetic on sulphonylureas or insulin; and interactions of artemether–lumefantrine with CYP3A4 inhibitors and inducers.

Efficacy and resistance: ACTs remain highly efficacious, with cure rates above 95% where the partner drug is effective. However, artemisinin partial resistance (delayed parasite clearance, mediated by Pfkelch13 mutations) is entrenched in the Greater Mekong subregion and has now emerged independently in Eritrea, Rwanda, Uganda, Ethiopia and Tanzania; chloroquine resistance in P. falciparum is universal in India, and sulfadoxine–pyrimethamine resistance is established in the north-east. Efficacy is monitored through therapeutic efficacy studies every 24 months at sentinel sites.

Chemoprophylaxis for travellers to endemic areas (Government of India recommendations): short-term (< 6 weeks) — doxycycline 100 mg daily, started 2 days before travel and continued 4 weeks after leaving; long-term (> 6 weeks) — mefloquine 250 mg weekly, started 2–3 weeks before and continued 4 weeks after. Atovaquone–proguanil (daily, from 1–2 days before to 7 days after) is the best-tolerated option internationally and the preferred choice for short trips and for older travellers because of its short post-travel tail and few interactions.

Terminal prophylaxis with primaquine (or a single dose of tafenoquine) after leaving an area endemic for P. vivax or P. ovale, subject to G6PD status, prevents late relapse.

Vector control and personal protection remain the backbone: long-lasting insecticidal nets (LLINs), indoor residual spraying, larval source management, repellents, screened housing and full-sleeved clothing after dusk. Under India's programme these are delivered through ASHA-led surveillance with rapid diagnostic tests and radical treatment at village level.

Vaccines — RTS,S/AS01 (Mosquirix) and R21/Matrix-M are WHO-recommended for children in areas of moderate-to-high transmission; the latter is manufactured by the Serum Institute of India. Neither has any role in adult or geriatric practice, and neither is used in India, where transmission is low and the goal is elimination.

Programmatic framework in India: the National Framework for Malaria Elimination (2016–2030) and the National Strategic Plan (2023–2027), delivered by the National Centre for Vector Borne Diseases Control (NCVBDC, formerly NVBDCP), categorise districts 0 to 3 by annual parasite incidence, with Category 0 districts (zero indigenous cases) entering prevention of re-establishment and eligible for subnational verification. By end-2025, 160 districts across 23 states/UTs had reported zero indigenous cases.