presentation on malaria - treatment and drug resistance - on the basis of microbiology

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