By NewsDesk  @infectiousdiseasenews

From a press release from Juntendo University in Bunkyo City, Tokyo (computer translated):

Malaria is transmitted from person to person through mosquitoes and causes more than 400,000 deaths each year. Although there are currently effective treatments, there is always concern about the emergence of drug-resistant Plasmodium malaria. Meanwhile, Professor Toshihiro Mita of the Department of Tropical Medicine and Parasitology discovered the world’s first drug-resistant Plasmodium in Africa, which had been found only in parts of Southeast Asia. We are conducting research, including field research, to prevent the spread of drug-resistant malaria.

Malaria is one of the three major infectious diseases in the world, along with HIV / AIDS and tuberculosis. It is prevalent in tropical and subtropical regions of Asia, Oceania, and Central and South America, mainly in Africa, causing more than 200 million new infections and killing about 430,000 people a year (November 2018 statistics).

The United Nations’ SDGs (Sustainable Development Goals), the third goal of “securing healthy lives and promoting welfare for all people of all ages,” also states that “AIDS, tuberculosis, and malaria by 2030.” And eradicate infectious diseases such as neglected tropical diseases. ” Malaria control is recognized as an issue that needs to be addressed on a global scale.

As you can see, malaria is a terrifying infectious disease, but there are very effective silver bullets. Artemisinin, currently used as a first-line drug, is an antimalarial drug developed in China in the 1970s. The combination therapy, mainly artemisinin, dramatically reduced the number of malaria deaths. The discoverer of artemisinin was highly praised for his achievements and received the 2015 Nobel Prize in Physiology or Medicine.

However, no matter how effective the drug is, there is a risk that some Plasmodium malaria with drug resistance (AMR) will not work. Looking back on the measures against malaria so far, the number of deaths of all three drugs, chloroquine, pyrimethamine, and sulfadoxin, which were considered to be malaria silver bullets, increased at a stretch due to the emergence of drug-resistant protozoans. bottom. All of these drug-resistant protozoans emerged in Southeast Asia and then spread to Africa all at once.

Artemisinin also began to appear in parts of Southeast Asia around 2007, and has spread to the Mekong River basin in the next few years. However, there was no report in Africa, which accounts for 90% of malaria patients, and it was thought that resistant protozoans had not yet appeared.

Therefore, our research group conducted a survey in the city of Guru in the northern part of the Republic of Uganda for three years from 2014 to 2017. By increasing the number of protozoans in a special in vitro culture medium and examining the efficacy of artemisinin, we discovered that artemisinin-resistant protozoans have emerged in Africa for the first time in the world.

The fact that it is found in vitro does not prove that it is actually resistant to local humans. Africans, in particular, have acquired immunity to malaria, which can also eliminate resistant Plasmodium from the body. Therefore, over the three years from 2017, we conducted a more detailed survey of 240 malaria patients. As a result, it was found that 14 people, or 5.8% of the subjects, met the clinical artemisin resistance criteria set by WHO. The results of this study revealed that artemisinin-resistant protozoans actually develop resistance in Africans.

n the survey from 2017, we also performed genome analysis and succeeded in identifying two mutations (A675V, C469Y) that occurred in Kelch13 , which is the responsible gene involved in artemisinin resistance . Protozoans with these mutations clearly have high levels of resistance and are clearly important for resistance. We also found that these mutations, which were not seen in 2015, surged to 16% in 2019, and we must take immediate action.

The gene mutation identified this time can be used as a molecular marker for early diagnosis. By using these mutations as molecular markers, we are aiming to establish a genetic diagnostic method that can easily and quickly detect artemisinin resistance by examining a single drop of blood. In the future, we expect that it will be possible to have only blood collected locally and to diagnose the emergence and spread of drug resistance in Japan based on the samples sent.

If the number of resistant protozoans increases in a certain population, the resistant protozoans will spread like ripples around it. Even in the case of past remedies, it has spread throughout Africa in this way and can no longer be used as a remedy. Our study found that drug resistance spread rapidly in northern Uganda, but has not yet been seen in southern Uganda and has not crossed national borders. If so, measures are needed to contain it at this stage.

In addition to the selection and spread of resistant protozoans that have a strong ability to infect in the protozoan population, the cause of the spread of resistant protozoans must also be considered as the possibility of “inappropriate drug use”. At our research site in Uganda, for a period of time, we distributed a three-piece set of antibiotics, antipyretics, and malaria remedies to various places so that we could take them immediately when we had a fever. In Africa, it is common to think of “fever = malaria” and take these medicines as soon as you have a fever. Repeated doses of artemisinin in such situations that are not originally needed may contribute to the development of drug resistance.

Similar problems are being seen in developed countries around the world, including Japan. We treat infectious diseases such as bacteria, viruses, and parasites with antibiotics, and repeated such treatments increase the number of drug-resistant bacteria, and by 2050, drug resistance. There are even warnings that the death toll from bacteria will exceed the death toll from cancer.

It is very difficult to control drug use in the presence of people who actually die from malaria infection, but proper use of the drug is important to prevent the spread of drug-resistant protozoans.

Malaria, on the other hand, is not always considered a scary illness. In Africa, which accounts for 90% of malaria-infected people, most adults are repeatedly infected with various types of Plasmodium and have acquired strong immunity. People who are already immunized will not swell when bitten by a mosquito, will not feel itchy, and can eliminate Plasmodium from their bodies. However, it becomes more severe when a child who does not have sufficient immunity becomes infected with malaria. More than half of the people who die of malaria are children under the age of five.

One year, a mother with a small child came to the hospital we were investigating. The mother seems to have lost seven children by the age of two, and the eighth child in front of her is having a fever at that age. I will die again, “he cried and asked for help. The current situation in Africa is still so harsh.

Even adults have a very troublesome condition of getting immunity halfway. This is because the protozoan is in the body and becomes a “carrier” that is transferred to someone through a mosquito, even though the person does not have any symptoms when infected. Plasmodium malaria is a very cunning parasite that, when unable to infect this host, transforms itself into a mosquito to grow offspring. In that way, we must fight against the malaria protozoan that spreads more and more.

Tropical medicine and malaria research are not major fields in Japan, but they are very actively researched in Europe and the United States, and they are very competitive research areas. Under such circumstances, Juntendo University’s research on malaria drug-resistant protozoa is undoubtedly one of the highest in the world.

After clinical practice in gastroenterology for about 9 years, I entered a laboratory studying malaria with the desire to contribute to medical care in developing countries. It happened that the malaria drug resistance study was recommended, but while conducting field surveys in various parts of Africa, I became more and more enthusiastic about this field while interacting with local patients.

Drug resistance is a phenomenon in which a target microorganism evolves at a visible speed. In addition, in tropical medicine, the human beings who are patients, the insects that mediate, and the environment related to public health are intricately intertwined, and it is the real pleasure to be involved as a medical specialist.

Of course, as a medical professional, I want to reduce the number of people who die of malaria as much as possible. As an initiative to eliminate malaria, research is being carried out focusing on the three pillars of vaccine development, therapeutic drug development, and drug resistance countermeasures, but in the current situation where effective vaccines have not been established, existing therapeutic drugs are being used. It is very important to take drug resistance measures so that you can use it properly. Drug resistance is a problem that can occur in any infectious disease, not just malaria, so we hope that our research will put an end to the problem of drug resistance.