Malaria: antimalarial and antiparasitic resistance

What is the state of play after ten years of funding to respond to malaria in the region? Is it a success story?

François Nosten: To be able respond to this, it is necessary to distinguish between Plasmodium falciparum malaria and Plasmodium vivax malaria.

In terms of Plasmodium falciparum, the situation has improved in relation to mortality and morbidity. The figures available do not necessarily reflect the reality, but feedback (epidemiological or treatment research activities, etc.) does indicate a decrease in the number of cases. Having said that, resistance continues to worsen. In Cambodia, for example, Plasmodium falciparum strains are more multi-resistant today than 10 or even 20 years ago, so there are fewer cases but more resistant parasitic outbreaks. Therefore, we can’t talk about it in terms of “success.” If there were no Plasmodium falciparum at all, we would be talking about success.

In terms of Plasmodium vivax, many infections are still happening in the Mekong region and, more generally, in Asia and India. It is a more complicated parasite to eliminate.

In conclusion, we can say that investments have had an impact, but malaria still remains an issue in Southeast Asia. From malaria’s history, we have learned that it is a disease that can come back suddenly and have considerable impact. This has been observed in the past, so we need be careful not to claim victory too soon because there are mixed results.

Is it true to say the “last mile” to defeat this disease is the hardest to achieve?

F. N: We need to be careful of the idea of the “last mile.” In recent years, I have felt on various occasions that we’d reached the last mile, but we need to continue our work until the battle is won. Political contexts and the COVID-19 crisis mean there is the potential for epidemic resurgence and for transmission to start up again. It will be necessary to continue working for several more years.

In Thailand, for example, it is unlikely that Plasmodium falciparum will return and cause a devastating epidemic in the next five years, but that is not only because the “last mile” has been reached but also because Thailand has a much stronger health system than neighboring countries. If, however, a problem arose on one of its borders, it would be fairly quickly contained. On the other hand, Cambodia, Laos, and Myanmar still need to be monitored.

In Karen state, Myanmar, the Plasmodium falciparum elimination program showed very promising results in the early years and then slowed sharply. We are searching for the last few sites and cases, so it feels like we are close to achieving the goal, but the geopolitical context and the COVID-19 crisis mean the potential for resurgence is worrying. We will have to work for several more years; the last mile is far from being reached.

Fortunately, we have seen progress and advances, and we have learned a lot about malaria in the region. We are moving in the right direction, but it is still too early to claim victory.

What makes Plasmodium vivax so different from Plasmodium falciparum?

F.N: Plasmodium vivax has an additional stage in its cycle that Plasmodium falciparum does not have; an asymptomatic liver stage. Infected people can remain with Plasmodium vivax at this stage for months or even years without symptoms. There are no markers, diagnoses, or tests that enable us to identify people with Plasmodium vivax at the liver stage. There is another complication, this liver stage of the disease can only be treated with the use of a single drug, primaquine. It has a very low level of tolerance among certain population groups, which means that it cannot be administered in large quantities to everyone.

Plasmodium vivax is, therefore, more difficult and takes much longer to eliminate than Plasmodium falciparum.

Although the mortality rate is lower than Plasmodium falciparum, Plasmodium vivax is a crippling parasitic disease that causes miscarriages in pregnant women. It has an impact on society.

What is the malaria context like in Myanmar today? What are the risks of concern?

F.N: Little is known about the malaria context in the country. The reality is that health facilities are not well maintained, communications are impaired, and supplies are compromised. There is a risk that infections will rise again as the population cannot be screened, treated, or protected. There may be an outbreak of Plasmodium falciparum during the next rainy season, but that does not mean we will be informed.

There is also a risk of epidemic rebound in Vietnam and Cambodia, as if resistance to treatment continues to increase, the number of infections could rise again as it did in the 1990s. Many observers are working on the issue in these countries, and early warning signs would be detected. Also, malaria treatments such as ACT (artemisinin-based combination therapy), which contain artemisinin, are available, and studies are currently being carried out on triple combination therapies.

| Further reading: “The Mekong Malaria Elimination Programme,” Bulletin 10, March 2022.