What is the organisms of malaria? Signs and symptoms of malaria Prevention of malaria? Write anti malarial drugs.1+5+5+2

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Malaria - Complete Overview

Source: Harrison's Principles of Internal Medicine 22E (2025, McGraw Hill Medical), Chapter 231

1. Organism of Malaria (1 mark)

Malaria is caused by protozoan parasites of the genus Plasmodium, transmitted to humans through the bite of an infected female Anopheles mosquito.

Six species cause human malaria:

Species	Key Feature
P. falciparum	Most deadly; causes >80% of infections and 90% of deaths in sub-Saharan Africa; can invade any erythrocyte
P. vivax	Common in Central/South America and Asia; forms dormant hypnozoites causing relapses
P. ovale (curtisi & wallikeri)	Two morphologically identical sympatric species; also forms hypnozoites
P. malariae	Found in most endemic areas; 72-hour erythrocytic cycle
P. knowlesi	Monkey malaria parasite; found in Southeast Asia; can cause severe disease
P. simium / P. cynomolgi	Occasional human infections from monkey reservoirs

P. falciparum is the most dangerous. P. vivax and P. ovale cause relapses due to dormant liver forms called hypnozoites.

2. Signs and Symptoms of Malaria (5 marks)

Classic Presentation

The typical malarial attack occurs in three stages:

Cold stage - sudden onset of shaking chills, rigors
Hot stage - high fever (up to 40-41°C), headache, flushing
Sweating stage - profuse sweating, temperature returns to normal, patient feels exhausted

Common Symptoms

Fever - classically periodic: every 48 hours (tertian) in P. vivax/ovale, every 72 hours (quartan) in P. malariae; irregular in early P. falciparum
Headache - often severe
Myalgia and arthralgia - generalized body pains
Malaise and fatigue
Nausea, vomiting, anorexia
Abdominal pain and diarrhea
Pallor - due to hemolytic anemia
Splenomegaly - in repeated or chronic infections
Hepatomegaly with mild jaundice

Signs/Symptoms of Severe (Falciparum) Malaria

Manifestation	Description
Cerebral malaria	Unarousable coma, Glasgow Coma Score <11; diffuse symmetric encephalopathy; seizures (~50% of children)
Severe anemia	Hematocrit <15% or Hgb <5 g/dL; normochromic, normocytic
Acidosis	Arterial pH <7.25, deep labored "respiratory distress" breathing
Hypoglycemia	Blood glucose <2.2 mmol/L; especially in children and pregnant women
Acute kidney injury	Oliguria, rising creatinine
Pulmonary edema / ARDS	Oxygen saturation <92%, very high mortality
Abnormal bleeding / DIC	Spontaneous bleeding, petechiae
Hyperparasitemia	>5% parasitized RBCs; poor prognostic sign
Hemoglobinuria (blackwater fever)	Massive intravascular hemolysis; dark/black urine
Prostration	Inability to sit unaided in older children/adults
Jaundice	Bilirubin >50 mmol/L; hemolytic + hepatic components

3. Prevention of Malaria (5 marks)

A. Personal Protection Against Mosquito Bites

Insect repellents: DEET 10-35% applied to exposed skin (or 7% picaridin if DEET is not tolerated)
Insecticide-treated bed nets (ITNs): Long-lasting ITNs (LLINs) treated with pyrethroids - reduce all-cause child mortality in Africa by ~20%. Newer nets combine pyrethroids with chlorfenapyr or pyriproxyfen to counter insecticide resistance
Protective clothing: Long sleeves and trousers, especially from dusk to dawn (peak mosquito feeding time)
Indoor residual spraying (IRS): Spraying homes with insecticides as part of integrated vector control programs

B. Environmental / Vector Control

Elimination of mosquito breeding sites (standing water, swamps)
Larviciding - treating water bodies to kill larvae
Biological control methods

C. Chemoprophylaxis (for travelers and high-risk groups)

Drug	Regimen	Area
Atovaquone-proguanil	Daily, start 1-2 days before travel, stop 7 days after	All areas including chloroquine-resistant regions
Mefloquine	Weekly, start 2-3 weeks before travel	Most endemic areas
Doxycycline	Daily	Chloroquine/mefloquine-resistant areas
Chloroquine	Weekly	Chloroquine-sensitive areas only
Primaquine	Daily	P. vivax-endemic areas; requires G6PD testing first

D. Intermittent Preventive Treatment (IPT)

IPTp - Intermittent preventive treatment in pregnant women (sulfadoxine-pyrimethamine each antenatal visit after 1st trimester)
IPTi - In infants at immunization visits
Seasonal malaria chemoprevention (SMC) - In high-transmission Sahel regions, children 3 months to 5 years receive monthly amodiaquine + SP during peak transmission season

E. Vaccination

RTS,S/AS01 (Mosquirix) and RTS,S/Matrix-M - Pre-erythrocytic vaccines recommended by WHO for deployment in young children in endemic areas; provide partial, relatively short-duration protection against P. falciparum
An irradiated live sporozoite vaccine (PfSPZ) is in late-stage development

4. Antimalarial Drugs (2 marks)

Major Classes

1. Artemisinin Derivatives (first-line)

Artesunate (IV/IM - drug of choice for severe malaria)
Artemether (IM)
Dihydroartemisinin (oral)
Mechanism: produce free radicals that damage parasite proteins; act on all erythrocytic stages

2. Artemisinin-Based Combination Therapies (ACTs) - WHO first-line for uncomplicated falciparum malaria

Artemether-lumefantrine
Artesunate-mefloquine
Dihydroartemisinin-piperaquine
Artesunate-amodiaquine
Artesunate-sulfadoxine-pyrimethamine
Artesunate-pyronaridine

3. 4-Aminoquinolines

Chloroquine - for P. vivax, P. ovale, P. malariae (and rare chloroquine-sensitive P. falciparum); acts by inhibiting heme detoxification
Amodiaquine - used as ACT partner drug

4. Quinoline Methanols

Quinine / Quinidine - for severe malaria when artesunate unavailable; IV quinine dihydrochloride
Mefloquine - oral; used for prophylaxis and as ACT partner

5. 8-Aminoquinolines

Primaquine - only drug active against hepatic hypnozoites (radical cure of P. vivax/P. ovale); also a gametocytocide; requires G6PD screening before use
Tafenoquine - once-weekly single-dose alternative to primaquine for P. vivax radical cure

6. Antifolates

Pyrimethamine + Sulfadoxine (SP / Fansidar) - used in IPTp for pregnant women; resistance widespread
Proguanil - mainly used in combination with atovaquone

7. Hydroxynaphthoquinone

Atovaquone-Proguanil (Malarone) - highly effective causal prophylaxis and treatment; acts on mitochondrial electron transport; expensive

8. Tetracyclines (used as partner drugs, not alone)

Doxycycline - prophylaxis and combination treatment; avoid in pregnancy and children <8 years
Tetracycline - similar use

Key Points to Remember:

WHO recommends ACT as first-line for all uncomplicated P. falciparum malaria
IV Artesunate is the drug of choice for severe malaria (35% mortality reduction vs. quinine in Asian adults)
Primaquine is the only agent that achieves radical cure for P. vivax and P. ovale by eliminating hepatic hypnozoites
Artemisinin resistance has emerged in Southeast Asia (Greater Mekong Subregion) and is now appearing in East Africa - a major global health threat

Harrison's Principles of Internal Medicine 22E (2025), Chapter 231: Malaria

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