Malaria purity in the biosafety laboratory of the Center for Global Health Drug Discovery in Beijing on April 3, 2024. Photo by Southern Weekly reporter Wu Xiaofei
April 26, 2024, is the 17th National Malaria Day. Malaria is a parasitic disease caused by the bite of a mosquito infected by the malaria parasite, which mainly includes vivax malaria, malaria ovale, malaria and falciparum malaria according to the species of protozoa. This ancient infectious disease has been plagued by humans for thousands of years, and people still can't completely get rid of it, and malaria is still widespread around the world. According to the World Malaria Report 2023 (the Report), the total number of malaria cases worldwide in 2022 was about 249 million, including 608,000 deaths.
After several generations of unremitting efforts, the number of malaria cases in China has changed from 30 million to 0, and remarkable achievements have been made in prevention and control. In June 2021, the World Health Organization (WHO) officially certified China as achieving malaria elimination, making it the first country in the Western Pacific region to eliminate malaria in more than 30 years.
But elimination is not the same as elimination. In addition to the long-term threat of malaria retransmission in China from common risk factors such as global warming, imported cases, and sudden infectious diseases, China also faces endogenous problems such as the loss of professional talents, the shortage of funds, and the deterioration of front-line doctors' awareness and ability to diagnose and treat the disease. The theme of this year's National Malaria Day is "Preventing the Re-spread of Malaria and Sustaining Elimination Gains".
"China has achieved malaria elimination through the implementation of the Malaria Elimination Action Plan, while some developed countries have gradually eliminated malaria by improving their comprehensive capabilities such as urbanization and medical conditions. This means that after the elimination of malaria, not only must we not reduce the level of prevention and control, but also improve the level of scientific research and medical care to deal with more complex imported cases, otherwise malaria is likely to return. Gao Qi, a member of the World Health Organization's Malaria Policy Advisory Committee and head of the National Expert Group on Malaria Elimination, told Southern Weekend on April 21, 2024.
Climate warming, mosquito resistance, imported from abroad
The prevention and control of infectious diseases are mainly affected by factors such as the source of infection, the vector of transmission, and the susceptible population. The malaria parasite, the source of malaria, has become resistant to most antimalarial drugs, and it is especially alarming to the antimalarial "killer" artemisinin.
The Report found that Plasmodium parasites of falciparum malaria have become resistant to artemisinin and its compatibles throughout the Greater Mekong Subregion, affecting treatment outcomes and prolonging treatment cycles for malaria patients, which also increases the risk of retransmission due to imported cases in areas where malaria has been eliminated.
Zhang Wenhong et al. from the National Center for Infectious Diseases (Shanghai) pointed out that due to the lack of understanding of global malaria drug resistance, some doctors may have problems such as ineffective administration, wrong administration or even overdose administration of drug-resistant Plasmodium parasites in clinical diagnosis and treatment, which will lead to malaria treatment failure and even patient death, and in the long run, may also lead to a decrease in malaria susceptibility to antimalarial drugs and the emergence of drug-resistant strains of malaria parasites.
Malaria is transmitted mainly by mosquitoes. Global warming will dramatically change the area, density and season of mosquitoes. The ideal breeding and survival temperature for mosquitoes is 20-27 degrees Celsius, and rising temperatures may make otherwise cooler, malaria-scarce areas more suitable for mosquitoes to survive, or lead to longer seasons suitable for mosquito breeding, which in turn can increase the probability of malaria transmission.
"In China, the malaria epidemic in the Huanghuai Plain used to be from July to September, but in recent years, as the climate has warmed, mosquitoes have survived from May to October and even November, and this extended season has created a new risk for malaria transmission. Gao Qi said.
In addition, a warming climate will lead to frequent extreme weather and frequent rainfall at lower latitudes, which also creates an ideal environment for mosquitoes to breed. According to the report, in 2022, excessive rainfall and flooding caused by extreme weather caused by extreme weather in Pakistan facilitated mosquito breeding, leading to a malaria outbreak in the country, with the total number of cases increasing by 2.1 million compared to 2021.
For China, it mainly affects cities in the southern region. "In places like Hainan and Yunnan, where water after frequent precipitation facilitates the laying of eggs, there are more mosquitoes in these areas than before, which in turn affects the spread and epidemic of malaria. Gao Qi said.
Gao Qi stressed that the changes brought about by global warming need to be paid special attention, and there are similar "lessons" in history. For example, in 2002, the national malaria epidemic fluctuated significantly, with an increase of 68.2 per cent compared to 2001. The incidence of malaria in 13 provincial-level administrative regions, including Anhui, Hunan and Jiangsu, has increased to varying degrees, which may be closely related to global warming.
On November 27, 2023, the WHO also called for attention to the impact of climate change on health, especially mosquito-borne infectious diseases, at the 28th Conference of the Parties to the United Nations Framework Convention on Climate Change.
It is worth mentioning that mosquitoes are now resistant to most insecticides. The scientific community has confirmed that malaria-carrying mosquitoes (Anopheles) have developed strong resistance to pyrethroids, the active ingredient of the most commonly used insecticides.
"Mosquito resistance is mainly related to the use of agricultural insecticides, including the type, dose, concentration of insecticides, etc., if a certain insecticide is frequently used in agriculture, then mosquitoes may become resistant to this type of insecticide, which brings great challenges to the follow-up mosquito prevention and control work, and will eventually affect the prevention and control of malaria. Gao Qi introduced.
All people can get malaria. For areas that have eliminated malaria, the biggest challenge comes from imported sources of infection, including positive patients who have been infected with malaria (including symptomatic patients and asymptomatic carriers) and positive mosquitoes infected with Plasmodium.
In 2022, malaria is still endemic in 85 countries around the world, and the current malaria cases in China are mainly imported from abroad. According to data from the Jiangsu Institute of Schistosomiasis Control, from February 2020 to September 2023, a total of 4,561 cases of schistosomiasis were reported in China, all of which were cases of foreign infection except for three cases of malaria malaria that had been dormant for a long time, and no local primary cases or secondary cases caused by imported cases were found, including about 300 cases of imported infection by positive mosquitoes.
A number of studies have shown that the risk of cross-border malaria transmission in China mainly comes from two aspects: first, the border area of Yunnan, especially the China-Myanmar border area bordering Myanmar, which poses challenges to the prevention and control of malaria epidemics due to the relatively volatile social environment and lack of medical resources in Myanmar, and the African countries along the "Belt and Road", which are also the "hardest hit areas" of malaria epidemics.
Mosquitoes bred using insect infertility technology at the China Atomic Energy Agency's Nuclear Technology (Sterile Insects) Research and Development Center, Dongguan, March 28, 2024. Photo by Southern Weekly reporter Zhao Ming
"The God of Wealth follows the God of Plague"
In the stage of malaria elimination and after the elimination of malaria in China, there are still many cases of severe malaria and deaths every year, which are mainly related to misdiagnosis and mistreatment in medical institutions, in addition to the delay in medical treatment of patients themselves.
A 2023 survey by the Institute for Parasitic Disease Control and Prevention of the Chinese Center for Disease Control and Prevention found that nearly one-third of the malaria cases reported in China from 2017 to 2018 were not correctly diagnosed at the time of initial diagnosis, more than one-third of patients took more than two days from initial diagnosis to diagnosis, and only 89.4% of the species identification was consistent with the final review results. From 2013 to 2022, only 65.2% of the three malaria cases reported in mainland China were diagnosed with malaria for the first time, and 71.1% of the confirmed cases were consistent with the final review results.
Taking the case of imported malaria mainly falciparum malaria as an example, "if falciparum malaria cannot be detected and treated early, the deterioration of the condition will lead to the failure of multiple organs such as liver and kidney, and in severe cases, it will also lead to death." An infectious disease doctor at a tertiary hospital in central China said. Zhang Wenhong et al. also pointed out that "delayed diagnosis, delayed administration, non-standard use of antimalarial drugs, and insufficient rescue capacity for severe malaria are the key factors leading to malaria deaths." ”
However, in the real world, the level of awareness and vigilance of health care institutions about malaria still faces challenges. In the above study, the overall awareness rate of malaria prevention and control staff in some areas was less than 75.0%, of which the overall awareness rate of medical staff in county-level hospitals was less than 80%, and the overall awareness rate of staff in township health centers and village clinics was 67.0% and 56.2%, respectively.
Zhang Wenhong and others believe that in the misdiagnosis of medical institutions, clinicians are the ones who play a key role compared to inspectors. Clinicians need to think about the possibility of malaria when they see patients. In the real world, the symptoms of malaria are diverse, and if doctors only regard intermittent chills and fever as a manifestation specific to malaria, it may lead to missed diagnosis.
According to Gao Qi's analysis, the misdiagnosis and misjudgment of malaria cases in medical institutions are mainly related to the following factors. First of all, in the teaching stage, the teaching materials about malaria in China are still mainly based on the local malaria parasites and cases that have been eliminated in China, and the professional knowledge obtained by medical personnel does not match the diversity of imported malaria; secondly, with the elimination of malaria in China, medical personnel also lack enough cases to practice in clinical practice, and "a disease is rare to a certain extent, and it becomes a rare disease that is difficult to treat to a certain extent".
"The most important factor is that 'the God of Wealth follows the plague god', and government departments at all levels have significantly declined their attention to malaria prevention and control after malaria elimination, and their understanding of the risk of retransmission after malaria elimination is insufficient, and they do not pay enough attention to the current malaria prevention and control work. Gao Qi said.
The reality of malaria transmission is far from a state of peace of mind. Compared with many developed countries, a considerable proportion of China's population lives in rural areas, and the mosquitoes that transmit malaria are also active for a long time, and the risk of malaria infection still exists.
Lack of funding can lead to a number of problems. At the end of March 2024, when Southern Weekend reporters interviewed experts studying mosquito-borne infectious diseases in many places, many of the experts interviewed focused on Aedes mosquitoes, which transmits tropical diseases such as yellow fever and dengue fever, but rarely on Anopheles mosquitoes, which transmit malaria.
The transfer and loss of front-line testing personnel also make it difficult for the malaria laboratory testing team to operate efficiently. The investigation of the China Disease Control and Prevention also found that there are still some areas where the feedback of laboratory review results is not timely, which affects the accurate identification of malaria cases and standardized treatment.
Gao Qi has always been worried about the shrinking of the scientific research team, and in his opinion, the current scientific community's understanding of malaria is still insufficient, and it is not the time for "the sword to be put into the warehouse, and the horse to be released in the south mountain". For example, he said that there is still a lack of understanding of the risk of transmission of imported malaria strains through local mosquito vectors, the response strategies of malaria parasites to artemisinin resistance are not clear, and there is still a lack of effective means to prevent and control insecticide-resistant mosquitoes, especially Anopheles mosquitoes that transmit malaria by outdoor bites...... And all of these require continuous research by scientific researchers.
On March 28, 2024, at the China Atomic Energy Agency's Nuclear Technology (Sterile Insects) R&D Center, workers manually isolate male mosquitoes after being "sterilized". Photo by Southern Weekly reporter Zhao Ming
How can imported malaria be prevented from retransmission?
After the elimination of malaria in China, the first priority is to prevent imported retransmission. Gao Qi introduced that the current malaria cases in China mainly come from positive mosquitoes and positive patients infected with the malaria parasite, including those who have been infected with the malaria parasite and are still in the incubation period.
"The patient who bites directly after the positive mosquito enters the country is the first generation of cases, also known as imported secondary cases; the positive patient is bitten by a local mosquito and then bites a healthy person, and the healthy person is infected with malaria is a second-generation case, which also forms local transmission, according to the WHO standard, the occurrence of more than three second-generation cases in an area for three consecutive years is the reconstruction of the transmission chain. Gao Qi introduced that the focus of China's prevention and control is to block the case situation in the first generation of cases or second-generation cases, prevent import and re-transmission, and start emergency response to sudden epidemics once there are second-generation cases, so as to strictly prevent the reconstruction of the transmission chain.
Preventing the import and retransmission of malaria requires the joint efforts of the entire malaria prevention and control chain. "The development of specific work must be carried out with the attention of the decision-making department, the maintenance and strengthening of the scientific research team, and the professional training of front-line medical personnel, all of which require a certain amount of financial guarantee. Gao Qi said.
Gao Qi stressed that the top priority of malaria prevention and control is to improve the professional level of medical personnel. He suggested that the knowledge of malaria diagnosis and treatment should be included in the doctors' professional skills examination to strengthen their professional knowledge, that relevant training could also be carried out through academic exchanges and other organizations, and that rapid diagnostic reagents should be promoted to replace traditional microscopic testing in grassroots medical institutions at the county and township levels.
Cao Jun, director of the Jiangsu Institute of Schistosomiasis Control, also said that health authorities at all levels should conduct regular assessments of the effectiveness of malaria prevention and control systems in various regions. The assessment should focus on the implementation of post-elimination surveillance, the maintenance of capacity for the diagnosis and treatment of malaria cases and the management of outbreaks, as well as the corresponding staffing and funding. "Regular assessments help to urge localities to maintain malaria prevention and control capacity and quality, and to consolidate the gains made in malaria elimination."
In terms of scientific research, the scientific community is also carrying out some active exploration on the problem of antimicrobial resistance of mosquitoes. Wang Sibao's team at the Center for Excellence in Molecular Plant Science of the Chinese Academy of Sciences is conducting a study on "Blocking Malaria Transmission with Natural Antimalarial Commensants of Anopheles mosquitoes", which intends to use bacteria to kill the malaria parasites in infected mosquitoes to block malaria transmission through mosquitoes, rather than directly killing mosquitoes with insecticides, so as to improve the problems of insecticide-induced mosquito resistance and environmental pollution.
The project of "Research and Development of Efficient Real-time Outdoor Malaria Vector Mosquito Trapping and Monitoring Technology and Device" of Chen Xiaoguang's team at Southern Medical University is also progressing in an orderly manner, with the aim of developing an efficient trapping device to grasp the mosquito population density, daily activities and growth and decline in real time, and to provide scientific tools for outdoor malaria vector monitoring and control.
The project "Research and Development of Sterile Insect Technique for the Control of Urban Malaria Vector Anopheles szei", undertaken by Sun Yat-sen University and other institutions, aims to develop a specific and environmentally friendly sterile insect technology for the control of outdoor Anopheles mosquito vectors and to meet the challenges of outdoor malaria transmission.
China is also actively developing drugs to treat malaria. Tsinghua University, the Bill & Melinda Gates Foundation, and the Beijing Municipal Government have been developing a new antimalarial drug in recent years, which aims to shorten the three-day continuous medication cycle for malaria patients to a single dose, so as to solve the problems of poor compliance and the difficulty of a single dose in multi-medication patients.
Southern Weekly reporter Wu Xiaofei
Editor-in-charge: Tan Chang