Preventing malaria from occurring

Clinicians should focus on those clinical cases that passively come into contact with the health system. They need to be treated because malaria is a life-threatening disease that can kill in the absence of treatment.

Yet, if we had prevented malaria from occurring, we would have less cases to treat.

Strategies to prevent malaria can be put in place. Using bednets and other vector control strategies has already been discussed, and the malaria vaccine will be addressed later; for the moment, we will focus on the use of antimalarial drugs for preventive strategies.

There are currently ways of delivering antimalarials that will prevent people receiving those drugs from getting infected and from developing the disease.

If you are, for example, travelling to a malaria-endemic area, you are at high risk of developing severe malarial disease and therefore need to be protected beforehand. You will start taking an antimalarial drug as prophylaxis a few days before you travel and continue to take it while you are still exposed, and for a few more days after your return.

Why don't we do the same with native populations in malaria-endemic areas? The problem is that it is not sustainable to treat entire populations for their entire lives.

However, antimalarials could be delivered to those more at risk at key moments in which they have better access to the health system, thereby minimising the number of times that people have to take a drug.

These intermittent preventive treatments (IPTs) use sulfadoxine-pyrimethamine, or SP, a different drug to the one used for treating malaria cases so as to avoid interference between the two kinds (curative vs preventive) of drugs.

More on malaria prevention

“Preventive therapies are recommended for the most vulnerable groups in malariaendemic areas of sub-Saharan Africa: pregnant women, infants and children under 5 years of age.”

Source: Malaria prevention works, World Health Organization 2017, under the CC BY-NC-SA 3.0 IGO licence.

Read more: https://www.who.int/malaria/publications/atoz/malaria-prevention-works/en/

Three preventive strategies

Very young children, particularly infants, and pregnant women are both at very high risk of developing severe malarial disease.

How can we adequately target and access these vulnerable groups?

Both these groups have access to health interventions that have very good coverage in key moments of their lives: vaccination or antenatal consultations. What if we were to use those key moments in which children and pregnant women have access to the health system, to deliver an antimalarial preventive strategy?

Three strategies could be combined.

First: intermittent preventive treatment in infants (IPTi), “a full therapeutic course of antimalarial medicine delivered to infants through routine immunization services, regardless of whether the child is infected with malaria”. This has not yet been implemented on a large scale.

More on IPTi, its impact, its cost-effectiveness

“Intermittent preventive treatment in infants (IPTi) is a promising malaria control strategy. IPTi with sulfadoxine-pyrimethamine was safe and efficacious across a range of malaria transmission settings.”

Source: Aponte JJ, Efficacy and safety of intermittent preventive treatment with sulfadoxine-pyrimethamine for malaria in African infants: a pooled analysis of six randomised, placebo-controlled trials, Lancet. 2009 Oct 31;374(9700):1533-42. doi: 10.1016/S0140-6736(09)61258-7. Epub 2009 Sep 16.

Read more: https://www.thelancet.com/journals/lancet/article/PIIS0140-6736(09)61258-7/fulltext

Second: Intermittent preventive treatment of malaria in pregnancy (IPTp), “a full therapeutic course of antimalarial medicine given to pregnant women at routine antenatal care visits, regardless of whether the recipient is infected with malaria”.

Pregnant women are particularly at risk because of the particularities of the placenta against which the parasite has never been exposed. IPTp is currently implemented but suffers large coverage gaps (69% of pregnant women are not receiving the minimum of 3 doses that we know to work).

Read more: https://www.who.int/malaria/areas/preventive_therapies/pregnancy/en/.

There is a third preventive approach that can be used with drugs: seasonal malaria chemoprevention, or SMC. This is pretty much the same strategy for infants or pregnant women but utilising schools as the unit of delivery. SMC involves giving an antimalarial once a month during the rainy season, the period of greatest malarial risk, which is generally short (3–4 months).

About 14 million children are protected by this approach, but there are still 15 million children not receiving this treatment.

Read more: https://www.who.int/malaria/areas/preventive_therapies/children/en/.

CALL TO ACTION

IPT strategies and SMC have been shown to prevent malaria during infancy, childhood and pregnancy, but massive coverage gaps must be addressed urgently.

Malaria treatment

Drugs that cure malaria have been used for centuries, starting back in the 17th century with the use of cinchona bark to treat fevers, which later developed into quinine.

Other drugs have since periodically appeared for the treatment of malaria.

The science of treating malaria has developed in parallel to armed conflicts as malaria played a fundamental role in military history, decimating armies and often causing more casualties than enemy forces.

More on the history of malaria treatment

Quinine has been used to treat malaria for more than 400 years. In the 17th century, it was common for missionaries in South America to treat the disease using the bark of the cinchona (quina-quina) tree ground to a fine powder.

The 19th century was a turning point in the history of malaria treatment. Pharmacists Pelletier and Caventou managed to isolate quinine. Declining to seek a patent, they gave away their discovery as a gift to humanity and opened the door to much larger scale production of the drug.

Quinine also played a crucial role in the First World War, during which malaria took a heavy toll. More than 1.5 million soldiers were affected by the disease.

In the United States Army alone, 695,000 soldiers were infected with malaria during World War II. The development of pharmaceutical alternatives to quinine thus became a military objective of strategic importance, prompting the United States to launch an unprecedented campaign in search of new antimalarial drugs.

In 1946, after four years of intense research that involved the analysis of more than 14,000 compounds, the United States introduced a new synthetic antimalarial drug: chloroquine. With the advent of chloroquine, the World Health Organization was able to launch a global malaria eradication programme in 1955.

During the Vietnam War, malaria once again became a huge problem for both sides involved in the conflict. The treatments available at the time proved ineffective against the proliferation of resistant parasites. The result was the development of mefloquine, which proved effective against chloroquine-resistant parasites and was soon adopted throughout the world despite its neurological side effects.

At the same time, China launched Project 523, a secret military programme tasked with finding a new antimalarial drug to help their Vietnamese allies. Project 523 recruited 500 scientists, who analysed over 2,000 plant extracts. The result of this painstaking labour was the development of artemisinin, an extract of the plant Artemisia annua.

Source: ISGlobal, 2019.

Read more: https://malariatreatment.isglobal.org/.

The challenge of creating new drugs against malaria

The development of drug resistance from the parasite has systematically eliminated the possibility of using many of the drugs. Today we are left with a single family of drugs: the artemisinin derivatives, based on a herbal remedy that had been used for more than two thousand years, for the treatment of fevers in China.

More on artemisinin

Chinese scientist Tu Youyou – who was awarded the Nobel Prize in 2015 – discovered artemisinin. The term “qinghao” is a general synonym in Chinese for the herbs in the Artemisia family. Qinghao is one of the most common herbs to have been prescribed in traditional Chinese medical practice for over two thousand years. In Chinese medical terms, it offers the functions of clearing deficient heat, cooling and detoxifying blood, eliminating osteopyrexia and fever, freeing from summer heat, ceasing the recurrence of malaria fevers, removing jaundice, etc.

Source: Tu Youyou, Nobel Lecture, Institute of Chinese Materia Medica, China Academy of Chinese Medical Sciences, Beijing, China, December 7, 2015.

Read more: https://www.nobelprize.org/uploads/2018/06/tu-lecture.pdf.

Drugs against recurrent malaria

Two of the species causing malaria – Plasmodium vivax and Plasmodium ovale – have the unique characteristic of causing relapsing episodes after the initial infection. The use of current antimalarial therapies is only effective against the asexual stages in the blood, but not against the dormant stages in the liver.

For this, a different family of drugs, the 8-aminoquinolines, is needed. However, these drugs have adverse effects, particularly among individuals who have an enzymatic deficiency called G6PD. In such patients (representing in some countries up to 25% of the population), the use of these drugs to clear hypnozoites can be associated with life-threatening hemolysis, and therefore needs to be administered with caution after screening for this deficiency.

Pamaquine, the first drug developed to prevent recurrent episodes of malarial fever that affect patients infected by P. vivax or P. ovale, was synthesised in 1924. Its use was, however, associated with serious adverse effects. It was replaced by primaquine, an antimalarial with a slightly lower grade of toxicity, created in 1946. Common side effects include vomiting, diarrhoea and stomach cramps.

In 2018, decades of research and development finally resulted in a new addition to this family of drugs: tafenoquine.

Which drugs can treat malaria?