This document discusses the treatment, drug resistance, and prophylaxis of malaria. It outlines the objectives of anti-malarial drug treatment, including eradicating the parasite from the blood and preventing relapse. For uncomplicated malaria caused by P. ovale, P. vivax and P. malariae, primaquine is used to prevent relapse along with other drugs. For complicated P. falciparum malaria, artemisinin combination therapy is recommended. The document also discusses factors that contribute to drug resistance in malaria parasites and methods for assessing drug resistance levels. Finally, it covers strategies for malaria prophylaxis, including chemoprophylaxis, vector control, and vaccination efforts.

1. Treatment, Drug Resistance
and Prophylaxis of Malaria
Vivek Rathi

2. Treatment of malaria
Anti-malarial drugs are used with various objectives –
 Therapeutic – to eradicate the erythrocytic cycle
 Radial cure – to eradicate the exo-erythrocytic cycle to prevent relapse
 Gametocidal – to destroy gametocytes to prevent mosquito transmission
 Chemoprophylaxis – to prevent infection in non-immune person visiting endemic
areas

3. Uncomplicated malaria
Positive for - P. ovale, P. vivax and P. malariae
Primaquine – to prevent relapse
In case of chloroquine resistance – Quinine
is given – 8 hourly for 7 days plus
doxycycline 100mg/day.
Complicated(falciparum) malaria
Artemisinin based combination therapy
(ACT) is given
Monotherapy with Artemisinin is banned
in India as it promotes resistance.

4. Severe Malaria

5. Anti-malarial drug Resistance
A drug resistant parasite will survive and multiply in a dosage that normally cures the
infection.
Resistance arises from spontaneous point mutations in the genome or gene
duplications.
3 levels of resistance are defined by WHO –
Following treatment,
1. R1 – parasitemia clears but recrudescence occurs
2. R2 – reduction but not a clearance of parasitemia
3. R3 – no reduction of parasitemia
Many strains of P.F. are MDR meaning as resistance to atleast 3 or more than 3 classes
of anti-malarial drugs.
Only sporadic cases of resistance to chloroquine/primaquine have been reported in
vivax malaria.

6. Factors that contribute to emergence of resistance –
1. longer half-life of drug
2. mutation in parasite gene
3. inadequate and irregular usage of drug
4. host immunity
Mechanism of drug resistance –
1. chloroquine resistance in P.F. – mutations in genes encoding for– PfCRT and PfMDR1
– result in impaired transport of chloroquine
2. Resistance to antifolates - like pyrimethamine – due to point mutation in DHFR gene
3. Resistance to artemisinin – not been reported yet, observed in experimental animals

7. WHO guidelines for assessing degree of resistance –
In-vivo methods – resistance assessed on 2 factors – persistence of clinical
manifestations, level of parasitemia
In-vitro tests –
1. WHO micro test – RPMI 1640 medium
2. ELISA – measurement of HRP-2 or pLDH
3. PCR – detect P.F. specific drug resistance genes
Prophylaxis against malaria
1. Chemoprophylaxis – travelers, migrant laborers, military personnel
(a) Short term – Doxycycline, 100mg/day, 2 days before and 4 weeks after
(b) Long term – Mefloquine, 5mg/kg weekly, 2 weeks before, during, 4 weeks after

8. 2. Vector control strategies –
(a) Anti-adult measures –
Residual spraying – DDT, malathion, fenitrothion
Space application- by ultra low volume method of pesticide dispersion
Individual protection – insecticide treated bed nets, repellents, protective clothing
(b) Anti-larval measures –
Larvicide – mineral oil or paris green
Source reduction – reduce mosquito breeding sites
Biological larvicide – Gambusia affinis(fish), Bacillus thuringiensis(bacteria)
3. Vaccination – till date no vaccine is licensed for human use
RTS, S/AS01 – only vaccine – used in children in sub-Saharan africa