Malaria: Past and Present

History of Treatment and Prophylaxis

This document gives a brief outline of anti-malarial drugs, brief historical notes and their usefulness today, when drug resistant strains of malaria have become a major problem. It is not a comprehensive history nor does it include a number of drugs which are no longer used.

Quinine

Quinine has been used for more than three centuries and until the 1930s it was the only effective agent for the treatment of malaria. Many of the anti-malarial drugs are derivates of this compound. It was found in the bark of the Cinchona tree and is the only drug, which over a long period of time, has remained largely effective in treating the disease. It is now only used for treating severe falciparum malaria, partly because of undesirable side effects. In Africa in the 1930s and 40s it was known for people to take quinine when they thought they had "a touch of malaria," and the association of repeated infections with falciparum malaria and inadequate treatment with quinine, resulted in the development, in some, of acute black water fever. A condition where the broken down red blood cells are being passed in the urine, which becomes very dark, almost black.

Chloroquine

A very effective drug both for treatment and prophylaxis. It was first used in the 1940s shortly after the Second World War and was effective in curing all forms of malaria, with few side effects when taken in the dose prescribed and it was low in cost. Unfortunately, most strains of falciparum malaria are now resistant to chloroquine and more recently chloroquine resistant vivax malaria has also been reported.

Alebrin (Mepacrine)

This drug was developed in the early 1930s. It was used as a prophylactic on a large scale during the Second World War (1939-45) and was then considered a safe drug. It had a major influence in reducing the incidence of malaria among troops serving in Southeast Asia. It is now considered to have too many undesirable side effects and is no longer used.

Mefloquine (Lariam)

First introduced in 1971, this drug is related structurally to quinine. The compound was effective against malaria, resistant to other forms of treatment, when first introduced and because of its long half life was a good prophylactic. Widespread resistance has now developed and this, together with undesirable side effects, have resulted in a decline in its use. Because of its relationship to quinine the two drugs must not be used together. There have been reports of various undesirable side effects including several cases of acute brain syndrome, which is estimated to occur in 1 in 10,000 to 1 in 20,000 of the people taking this drug. It usually develops about two weeks after starting mefloquine and generally resolves after a few days.

Halofantrin (Halfan)

Belongs to a class of compounds not related to quinine. It is an effective antimalarial drug introduced in the 1980s, but due to its short half life of 1 to 2 days, is therefore not suitable for use as a prophylactic. Unfortunately, resistant forms are increasingly being reported and there is some concern about its side effects. Halofantrin has been associated with neuropsychiatric disturbances. It is contraindicated during pregnancy and is not advised to women who are breastfeeding. Abdominal pain, diarrhea, puritus and skin rash have also been reported.

Malarone

This drug combination, called malarone, was released in the late 1990s. It is a combination of proguanil and atovaquone. Proguanil was first synthesized in 1946 and is still used as a prophylactic in some countries. Atovaquone became available in 1992 and when combined with proguanil there is a synergistic effect, and the combination is at the present time a very effective antimalarial treatment. The drug combination has undergone several large clinical trials and has been found to be 95% effective in otherwise drug resistant falciparum malaria. How long it will be before resistant strains of malaria appear remains to be seen. It has been claimed to be largely free from undesirable side effects, but it should be noted that proguanil is an antifolate. This is not likely to be a problem with a single treatment course of the drug but some caution should be exercised when using it for prophylaxis. At present it is a very expensive drug.

Artemisinin

Derived from a Chinese herbal remedy and covers a group of products. The two most widely used are artesunate and artemether. While they are widely used in Southeast Asia, they are not licensed in much of the Western World. A high rate of treatment failures has been reported and it is now being combined with mefloquine for the treatment of falciparum malaria.

Drug Resistance

Drug resistant malaria has become one of the most important problems in malaria control in recent years. Resistance in vivo has been reported in all antimalarial drugs, except artemisinin and its derivatives. Drug resistance necessitates the use of drugs which are more expensive and may have dangerous side effects. In some parts of the world, artemisinin drugs are the first line of treatment, and are used indiscriminately for self treatment of suspected uncomplicated malaria - so we can expect to see malaria forms resistant to artemisinin soon according to WHO.

 

The areas most affected by drug resistance are the Indo-Chinese peninsula and the Amazon region of South America. The problem of drug resistance can be attributed primarily to increased selection pressures on P. falciparum in particular, due to indiscriminate and incomplete drug use for self treatment. In areas such as Thailand and Vietnam, mosquitoes of the Anopheles dims and Anopheles minimus species spread the drug resistant parasites. These mosquitoes adapt their biting activity to human behavior patterns, and maintain intense transmission. Drug resistant P. falciparum was first reported in Thailand in 1961. Various P. falciparum "strains" have now attained resistance to all commonly used and generally available antimalarial drugs. In man, the problem of resistance to the common antimalarial drugs, such as chloroquine and the decreasing effectiveness of quinine, is mainly limited to P. falciparum infection; chloroquine remains the treatment of choice for P. vivax.

By Professor Paul Henri Lambert
First published 9 December 2003

 

| What is Malaria? | History | Global impact | Treatment | Further Reading