Malaria: treatment and prevention

Chemotherapy and chemoprophylaxis

• Antimalarial drugs have selective actions on the different phases of
the parasite life cycle
• Causal prophylaxis drugs prevent the establishment of the parasite
in the liver and blood schizontocidal drugs attack the parasites in
RBCs, preventing or terminating the clinical attack
• Tissue schizontocides act on pre-erythrocytic forms in the liver
• Gametocytocidal drugs destroy the sexual forms of the parasite in
the blood
• Hypnozoitocidal kills the dormant hypnozoites in the liver
(responsible for relapses in P. ovale and P. vivax)
• Sporontocidal drugs- inhibit the dev of oocysts on the stomach wall
of the mosquito that has fed on the human gametocytes carries so
that the mosquito cannot transmit the infection
• People who have by repeated exposure to infection, acquire a
degree of immunity can be cured or protected much more easily by
drugs than those who have not
 Uses of antimalarial drugs

Efficacy of antimalarial is determined by:-

• The spp of malaria parasites e.g. spp with hypnozoites stage are
eradicated by 8-aminoquinoline- primaquine or tafenoquine
• Parasites sensitivity to drugs:- Pf resistance to Chloroquine + SP
• The host’s degree of immunity to the parasite:- treatment of immune
vs treatment of non-immune
• Analysis of the benefits of treatment vs the risks of adverse effects
• Drug costs: many drugs are unaffordable to many patients
• Practicability of the treatment regimen: for both outpatient and in
patients treatment
The main uses of antimalarial drugs are:-
i. Protective (prophylactic)
ii. Curative (therapeutic):- therapy of established infection
iii. Preventive of transmission:- drug effects on gametocytes + interruption
of sporogony in the insect
 The main antimalarial drugs
• Artemisinins:- (derivatives- Artemether,arteether and artesunate)
Action:- destroy the parasites membrane by oxidative action
• Atovaquone:- affects the maturations of trophozoites and gametocytes of P.
falciparum
- Used in combination with proguanil for treatment and prophylaxis
of multiresistant falciparum malaria
• Lumefantrine:- used in combination with Artemether (Co-Artemether) for
the treatment of uncomplicated multiresistant falciparum malaria
• Chloroquine and Amodiaquine:-acts against stages of malaria lifecycle
which actively digest haemoglobin within the erythrocytes. The drug target
the food vacuole of the parasites
- The drugs are effective against P. vivax, P. ovale and P. malariae
- P. falciparum are resistant to Chloroquine
- Oral Chloroquine is used for the treatment and prophylaxis of vivax,
ovale and malariae malarias and for uncomplicated Chloroquine-sensitive
falciparum malaria
 The main antimalarial drugs
• Amodiaquine:- Chloroquine-resistant strains of P. falciparum may remain
sensitive to Amodiaquine
- Amodiaquine is no longer recommended for prophylaxis due hepatic
effects
• Clindamycin:- Lincosamide antibiotic and has blood schizontocidal
activity of against Pf and must be used in combination
- Is effective against multiresistant Pf in South America, Africa, Asia
• Halofantrine:- efficacy against the multidrug resistant Pf and is used in
combination with artemesinin derivatives. Monotherapy resistance have
been reported
• Mefloquine:- used for the prophylaxis and treatment of uncomplicated
multiresistant falciparum malaria
- In combination with artesunate- effective against uncomplicated
falciparum malaria in areas with Mefloquine resistance
• Primaquine and Tefenoquine:- Primaquine is used for the radical cure of
vivax and ovale malarias as a community transmission blocking
(gametocytocidal) drug against P. falciparum
 The main antimalarial drugs
• Tafenoquine:- hypnozoitocide, blood schizontocide and
gametocytocidal
• Proguanil and chlorproguanil:- Proguanil used in combination with
Chloroquine for the prophylaxis of mildly Chloroquine resistant
falciparum malaria and in combination with Atovaquone
• Pyrimethamine:- In combination with dapsone (Maloprim or
Deltaprim) is used as prophylaxis of mildly Chloroquine resistant
falciparum malaria
- Used in combination with sulfadoxine (Fansidar) or with sulfalene
(Metakelfin) for treatment of uncomplicated Chloroquine resistant
falciparum malaria
- Fansidar (SP) for IPTp-SP during pregnancy
• Pyronaridine:- used in both oral and parenteral forms for the
treament of chloroquine-resistant Pf malaria
- Used for treament of uncomplicated chloroquine resistant
falciparum malaria
 The main antimalarial drugs
• Quinine:- interferes with parasite metabolism of haemin, a toxic
product of haemoglobin digestion
- Is the drug of choice for the parenteral treatment of severe
and the oral treatment of uncomplicated chloroquine-
resistant falciparum malaria
- The drug is also recommend during pregnancy
• Sulphanamides and sulphones:- in combination with pyrimethamine
(e.g. Fansidar) are used for treatment of chloroquine-resistant
falciparum malaria OR Dapsone + Pyrimethamine (Maloprim) is
used for the prophylaxis of mildly chloroquine-resistant falciparum
malaria
• Tetracycline:- Used in combination with quinine in the treatment of
severe and uncomplicated multi-resistant falciparum malaria
- Doxycycline is used for the prophylaxis of multiresistant
falciparum malaria.
 Combination therapy
• Why combination? Monotherapy results in rapid dev. of
drug resistance
- Example the use of Mefloquine 25mg/kg parasite resistance
was 50% in 1994 and treatment was changed to mefloquine
25mg/kg + Artesunate 4 mg/kg and cure rate is 95%
- Artesunate rapid acting blood schizontocide reducing
parasite density + inhibitory effect on gametocytes
• An important aspect of combination therapy is mutual
simultaneous protection offered to each of the partner drugs.
No parasites is exposed to one drug in the absence of the
other.
• Further combination therapy allows the dose of individual
drugs to be reduced
 Drugs used in combination therapy
• In fixed ratio combination therapy- the two drugs are
formulated in a single tablet
1. Lumefantrine + artemether (Co-artemether)
2. Amodiaquine + artesunate (understand)
3. Sulphadoxine-pyrimethamine + artesunate
4. Artemether + Lumefantrine