PHWR Public Health Weekly Report

Malaria is transmitted through the bite of a female Anopheles spp. mosquito infected with a Plasmodium spp. protozoan. In all, five Plasmodium spp. can cause malaria in humans: Plasmodium falciparum, P. vivax, P. ovale, P. malariae, and P. knowlesi. P. falciparum is the most prevalent in Africa and is responsible for the majority of global malaria cases, often associated with severe complications and high mortality rates. In contrast, P. vivax, though causing less clinically severe infection, is the most widely distributed worldwide, with high prevalence in Asia, including Republic of Korea (ROK). P. ovale and P. vivax are less prevalent but persistent in several West African and Southeast Asian countries, while P. knowlesi is persistent only in a few Southeast Asian countries [1]. According to the World Health Organization (WHO), 249 million cases of malaria were reported in 85 countries worldwide in 2022. Of these, 93.6% occurred in Africa, 3.3% in the Eastern Mediterranean, 2.1% in Southeast Asia, 0.8% in the Western Pacific, and 0.2% in the Americas (Figure 1) [2].

Figure 1. Countries with indigenous cases in 2000 and their status by 2022
Reused from the report of World Health Organization, 2023 [2].

ROK experienced a peak of 4,142 malaria cases in 2000 following the re-emergence of P. vivax in 1993 at a military base near the North Korean border. Thereafter, the number of cases decreased to 385 in 2013. Recently, the number of cases decreased to 485 in 2019, 356 in 2020, and 274 in 2021, before increasing again to 381 in 2022 [3]. In North Korea, 1,819 cases of P. vivax infection were reported in 2020, marking a 91.7% decrease from 21,850 cases in 2012. However, the number of cases fluctuated, with 2,357 reported in 2021 and 2,136 in 2022 [2]. This study aimed to summarize the global malaria epidemic trends in 2022, the challenges faced by countries in combating the disease, and their efforts, based on the 2023 WHO World Malaria Report.

1. Highlights in 2022–2023

1) Operational strategy of the Global Malaria Programme

As global progress toward malaria eradication has stalled in recent years, a "business as usual" approach will leave many countries trapped in this ongoing struggle. Recognizing the need for a significant shift in the malaria response, the WHO and the Global Malaria Programme have developed a sectoral operational strategy for 2024–2030. This strategy focuses on four strategic goals: establishing norms and standards, fostering new tools and innovation, utilizing strategic information for impact, and providing strong leadership, with the fifth goal being to offer context-based support tailored to individual countries.

2) New World Health Organization recommendations

To prevent malaria in adults and children in areas where mosquitoes have developed resistance to pyrethroids, the WHO strongly recommends distributing pyrethroid-chlorfenapyr insecticide-treated mosquito nets (ITNs) and pyrethroid-only ITNs.

3) Distribution of malaria vaccines (RTS,S/AS01, R21/Matrix-M) and World Health Organization recommendations

Since 2019, the Malaria Vaccine Implementation Programme, managed by the WHO and funded by Global Alliance for Vaccines and Immunisation (GAVI), the Vaccine Alliance, has provided Ghana, Kenya, and Malawi with the malaria vaccine RTS,S/AS01 (RTS,S), which targets the sporozoite transmembrane protein. Since the WHO recommended about the use of RTS,S in October 2021, at least 28 African region countries have submitted applications to GAVI to introduce malaria vaccines, with applications in 18 countries ultimately approved for support. Given the limited initial supply of RTS,S, the first 18 million doses for 2023–2025 have been allocated to 12 countries. The first deliveries were made in the fourth quarter of 2023, with vaccinations expected to be completed in each country by early 2024.

In October 2023, R21/Matrix-M (R21) was named the second vaccine recommended by the WHO to prevent malaria in children living in high-risk areas. The introduction of the R21 malaria vaccine is expected to alleviate the shortage of the currently distributed RTS,S vaccine, ensuring an adequate supply for children in regions where malaria is a major public health concern. The WHO recommends using malaria vaccines (RTS,S or R21) to prevent P. falciparum in children living in malaria-endemic areas with moderate to high transmission rates. The next step for R21 distribution is completing the ongoing WHO prequalification to facilitate international procurement for wide-scale supply. The combined efforts of the WHO and GAVI members will greatly benefit countries seeking to introduce malaria vaccines.

2. Global Trends in Malaria Outbreaks

1) The status of malaria cases

In 2022, 249 million cases of malaria were reported globally across 85 countries and areas, including French Guiana, marking an increase of 5 million cases from 2021. The countries contributing most to this increase included Pakistan (+2.1 million cases), Ethiopia (+1.3 million cases), Nigeria (+1.3 million cases), Uganda (+597,000 cases), and Papua New Guinea (+423,000 cases). Compared to approximately 231 million cases in 2015, which was the baseline year for the Global Technical Strategy (GTS) for Malaria 2016–2030, an overall increase of 18 million cases was reported.

The incidence of malaria was 58 cases per 1,000 population at risk in 2022, showing stability over the past 3 years following a decrease from 81 cases per 1,000 population at risk in 2000 to 57 cases in 2019, with a slight increase of 3% in 2020. A total of 29 countries accounted for 95% of global malaria cases, with four countries—Nigeria (26.8%), the Democratic Republic of the Congo (12.3%), Uganda (5.1%), and Mozambique (4.2%)—accounting for nearly half of all global cases (Figure 2) [2]. The percentage of P. vivax infection cases decreased from approximately 8% (20.5 million cases) in 2000 to 3% (6.9 million cases) in 2022.

Figure 2. Global trends in distribution of malaria cases by country, 2022
Reused from the report of World Health Organization, 2023 [2].

Approximately 93.6% of the global malaria cases were reported in Africa, totaling approximately 233 million cases in 2022. The incidence was 232 cases per 1,000 population at risk in 2020 due to interruption of services during the coronavirus disease 2019 (COVID-19) pandemic, but it decreased to 223 cases in 2022. Cabo Verde reported zero indigenous malaria cases for 4 consecutive years, marking the end of the epidemic there.

Southeast Asia accounted for approximately 2.1% of global malaria cases, with a significant decrease of 76% from 23 million cases in 2000 to approximately 5 million cases in 2022. The incidence of malaria in the region dropped by 83%, from approximately 18 cases per 1,000 population at risk in 2000 to approximately three cases in 2022. However, despite the overall 11.9% decrease in the number of cases in Southeast Asia from 2021 to 2022, the number of cases and incidence increased in Bangladesh, Indonesia, Myanmar, and Thailand.

The Eastern Mediterranean experienced a 38% decrease in the number of malaria cases, from approximately 7 million cases in 2000 to approximately 4 million cases in 2015. However, this was followed by a 92% increase to 8.3 million cases from 2015 to 2022. From 2021 to 2022, Pakistan reported 2.1 million cases of malaria following devastating floods that affected more than 30 million people, marking a 25% increase in the region. Sudan is a major malaria-endemic country in the Eastern Mediterranean, accounting for approximately 41% of cases. Although the Islamic Republic of Iran had zero indigenous malaria cases for 4 consecutive years (2018–2021), 1,439 cases, including indigenous cases, were reported in 2022. Saudi Arabia reported zero indigenous malaria cases for 2 consecutive years.

In the Western Pacific, the number of malaria cases decreased by 29%, from 2.6 million in 2000 to approximately 1.85 million in 2022. Papua New Guinea accounted for nearly 90% of all malaria cases in the region in 2022. China was declared malaria-free in 2021, while Malaysia reported zero human malaria (P. falciparum and P. vivax) cases for 5 consecutive years, despite reporting 2,500 zoonotic malaria (P. knowlesi) cases in 2022.

In the Americas, the number of malaria cases decreased by 64%, from 1.5 million in 2000 to 550,000 in 2022. The Bolivarian Republic of Venezuela, Brazil, and Colombia accounted for 73% of all cases in the Americas. Argentina, Belize, El Salvador, and Paraguay were declared malaria-free in 2019, 2023, 2021, and 2018, respectively.

Malaria has been eradicated from Europe since 2015.

2) Malaria deaths

Malaria-related deaths have steadily decreased worldwide, from 864,000 in 2000 to 586,000 in 2015 and 576,000 in 2019. However, in 2020, the number of malaria deaths increased by 10% compared with the number in 2019, reaching an estimated 631,000. In 2022, the number of deaths decreased slightly to 608,000. The incidence of malaria deaths among children aged <5 years decreased from 87% in 2000 to 76% in 2022. Approximately 96% of global malaria deaths occurred in 29 countries, with four countries—Nigeria (31.1%), the Democratic Republic of the Congo (11.6%), Niger (5.6%), and Tanzania (4.4%)—accounting for just over half of all malaria deaths in 2022 (Figure 3) [2].

Figure 3. Global trends in distribution of malaria deaths by country, 2022
Reused from the report of World Health Organization, 2023 [2].

The number of malaria deaths in Africa decreased from 808,000 in 2000 to 548,000 in 2017, before increasing to 604,000 in 2020. By 2022, the number of deaths had fallen again to 580,000.

In Southeast Asia, the number of malaria deaths reduced by 77%, from approximately 35,000 in 2000 to 8,000 in 2022. Approximately 94% of all malaria deaths his region occurred in India and Indonesia.

In the Eastern Mediterranean Region, the number of malaria deaths decreased by 45%, from approximately 13,600 in 2000 to 7,500 in 2014. However, the number more than doubled to 15,900 between 2014 and 2022, with the majority of deaths occurring in Sudan, where approximately 90% of cases were due to P. falciparum.

In the Western Pacific, the number of malaria deaths decreased by 56%, from approximately 6,300 in 2000 to 2,600 in 2021. However, from 2021 to 2022, the number of deaths increased by 29% to 3,600, primarily in Papua New Guinea.

In the Americas, the number of malaria deaths decreased by 63% from 850 in 2000 to 343 in 2022. The mortality rate decreased by 71%, from 0.7 to 0.2 per 100,000 population at risk.

3) Exposure to malaria during pregnancy

In 2022, approximately 35.4 million pregnancies were reported in 33 moderate-to-high malaria-risk countries in Africa, with an estimated 12.7 million women (36%) exposed to malaria during pregnancy. By subregion, exposure to malaria during pregnancy was the highest in West Africa (39.3%) and Central Africa (40.1%), and the lowest in East and Southern Africa (27.0%). Without specific pregnancy-related interventions, approximately 914,000 newborns in these 33 countries might have been born with low birth weight due to malaria infection during pregnancy. Providing at least one dose of intermittent preventive treatment of malaria in pregnancy (IPTp) to every pregnant woman attending antenatal care (ANC) clinics can prevent an additional 60,000 cases of low birth weight. Increasing IPTp3 coverage to match the level of the first ANC visit and achieving similar increases in subsequent ANC clinic visits could prevent an additional 164,000 cases of low birth weight. Expanding IPTp3 coverage to 90% of all pregnant women would prevent an additional 229,000 cases of low birth weight. Given that low birth weight significantly increases the risk of neonatal and childhood mortality, preventing a substantial number of newborn cases of low birth weight can save many lives.

3. Malaria Elimination

The number of countries reporting fewer than 100,000 indigenous malaria cases increased from six in 2000 to 27 in 2022, indicating a slight decrease from the 28 countries in 2021. The number of countries with fewer than 10 indigenous cases increased from four in 2000 to 25 in both 2021 and 2022. Among malaria-endemic countries in 2000, 25 achieved zero indigenous malaria cases for 3 consecutive years from 2000 to 2022, with 12 of these countries being officially declared malaria-free by the WHO. While no countries were declared malaria-free in 2022, three countries—Azerbaijan, Belize, and Tajikistan—received malaria-free certification in 2023. Additionally, two countries—Egypt and Timor-Leste—submitted official requests for certification in 2023. Cabo Verde is nearing the final stage of the certification process, having reported zero indigenous cases for 4 consecutive years (Figure 4) [2].

Figure 4. Countries eliminating malaria since 2000
Reused from the report of World Health Organization, 2023 [2].

The WHO is developing guidelines to address border malaria, a persistent challenge in elimination of malaria and prevention of re-emergence. Bhutan, Saudi Arabia, and Suriname are actively implementing strategies to prevent the reintroduction of indigenous malaria cases after reporting zero indigenous cases for the first year. Despite 5 years of zero local transmission, the Islamic Republic of Iran is currently experiencing an outbreak of indigenous malaria cases. Frequent cross-border movement of people is suspected to have contributed to the introduction of cases and the further re-establishment of local transmission. In response, the WHO is developing guidelines to prevent the re-emergence of malaria, acknowledging existing policy gaps.

Launched in 2021, the Eliminating malaria 2005 (E-2025) initiative aims to eradicate malaria, succeeding the E-2020 initiative. The E-2025 initiative encompasses 25 countries and one area: Belize, Bhutan, Botswana, Cabo Verde, the Comoros, Costa Rica, North Korea, the Dominican Republic, Ecuador, Eswatini, French Guiana, Guatemala, Honduras, the Islamic Republic of Iran, Malaysia, Mexico, Nepal, Panama, ROK, Sao Tome and Principe, Saudi Arabia, South Africa, Suriname, Thailand, Timor-Leste, and Vanuatu (Figure 5) [2]. As a participant in E-2025, ROK has developed a second Malaria Re-elimination Action Plan and is working to reduce the number of malaria cases through collaboration among the private, public, and military sectors.

Figure 5. Countries and areas selected for the Eliminating malaria 2005 (E-2025) initiative (source: WHO estimates)
Reused from the report of World Health Organization, 2023 [2].

4. The High Burden-to-high Impact Approach

Since November 2018, all 11 high burden-to-high impact (HBHI) countries have been implementing activities across four key response elements: 1) political will and commitment from national to community levels; 2) strategic use of information to guide malaria control efforts; 3) improved technical and policy guidance at all levels; and 4) effective coordination and leadership. In 2022, Sudan joined the HBHI initiative, increasing the official number of HBHI countries to 12. However, full implementation in Sudan was hindered by the conflict that erupted in early 2023. The initial HBHI countries, including several additional countries in Africa and the Eastern Mediterranean, have started applying subnational tailoring (SNT) of interventions. SNT involves using local data and contextual information to identify the most effective combination of interventions and strategies for specific regions, aiming to achieve optimal impact on disease transmission and burden at a strategic level or within specific resource constraints. The adoption of SNT has led to the integration of data into regular decision-making processes, enhancing efforts to improve the regular collection, review, and quality of data.

5. Investment in Malaria Programs and Research

The GTS outlined the estimated funding required to meet the 2025 and 2030 goals. The total annual funding needed was estimated at USD 6.8 billion in 2020, increasing to USD 9.3 billion by 2025 and USD 10.3 billion by 2030. Additionally, USD 85 million was estimated to be needed annually for global malaria Research and Development (R&D) from 2021 to 2030. In 2022, the total funding for malaria control and elimination was estimated at USD 4.1 billion, increasing from USD 3.5 billion in 2021 and USD 3.3 billion in 2020. Despite this increase, the 2022 funding fell short of the USD 7.8 billion required to achieve the GTS milestones. The funding gap between the actual investment and the resources needed has continued to widen over recent years, increasing from USD 2.3 billion in 2018 to USD 3.7 billion in 2022. The United States contributed over USD 1.5 billion through planned bilateral funding and malaria-adjusted shares of multilateral contributions. The contribution of France, Germany, Great Britain, and Northern Ireland combined was over USD 400 million through bilateral and multilateral disbursements. Australia, Canada, and Japan each contributed approximately USD 100 million, with other members of the Development Assistance Committee and private sector contributors adding a combined USD 400 million. Of the USD 4.1 billion invested in 2022, more than three-quarters (80%) was allocated to Africa, with 4% each to Southeast Asia, the Eastern Mediterranean, and the Americas, and 2% to the Western Pacific. The remaining 6% of the total funding in 2022 was allocated to unspecified regions. The funding allocation increased significantly in Africa but remained stable in other WHO regions.

The total R&D funding for malaria amounted to USD 603 million in 2022, marking a decrease of more than 10% from the funding in 2021 and reaching its lowest level in the past 15 years. This decrease follows 4 consecutive years of declining funding since the peak in 2018. The drop was the most significant in the vaccine sector, which fell by 13% over 5 years, and in the basic research sector, which decreased by 20%. Medicines continued to receive the largest share of funding despite a 12% decrease. Conversely, funding for biologics continued to increase for the 4 consecutive years, increasing by more than 250% in 2022 to nearly 14 times the level in 2018. The Bill & Melinda Gates Foundation provided the first-ever funding for biologics clinical development with a $3.9 million grant to the Centers for Disease Control and Prevention (CDC) Foundation. Funding from the public sector in high-income countries fell by 18%, reaching its lowest level in over a decade, although these countries remained the primary source of malaria R&D funding. Funding from other sectors also declined, except for the private sector, which saw a rebound with an increase of USD 10 million in 2022.

6. Distribution and Coverage of Malaria Prevention, Diagnosis, and Treatment

1) Distribution and coverage of malaria prophylaxis

From 2004 to 2022, manufacturers delivered approximately 2.9 billion ITNs globally, with 2.5 billion (86%) shipped to sub-Saharan Africa. In 2022, approximately 282 million ITNs were supplied to malaria-endemic countries. Of the 260 million ITNs distributed to sub-Saharan Africa in 2022, nearly 51% were pyrethroid-piperonyl butoxide nets. In 2022, a total of 254 million ITNs were distributed globally through National Malaria Programmes (NMPs), with 235 million of these going to sub-Saharan Africa. From 2000 to 2022, the percentage of the population using ITNs increased significantly: from 2 to 49% for the general population, from 3 to 56% for children under 5 years of age, and from 3 to 56% for pregnant women.

The percentage of the global population at risk covered by indoor residual spraying (IRS) in malaria-endemic countries decreased from 5.5% in 2010 to 1.8% in 2022. Since 2016, coverage by IRS has remained stable, with less than 6% of the population in each region being protected. The global population covered by IRS fell from 153 million in 2010 to 62 million in 2022.

The average number of children treated with seasonal malaria chemoprevention (SMC) per cycle has steadily increased from approximately 200,000 in 2012 to 49 million in 2022. Nigeria experienced the highest increase, treating an average of 25.5 million children with SMC per cycle. In 2022, 17 countries implementing SMC in the Sahel and other malaria-endemic regions of sub-Saharan Africa received a total of approximately 200 million doses of SMC.

In the WHO Africa region, data from 33 countries indicated that 78% of pregnant women accessed ANC services at least once during pregnancy in 2022. Coverage with IPTp was approximately 64% for IPTp1, 54% for IPTp2, and 42% for IPTp3.

2) Distribution of malaria diagnostics and treatments

In 2022, manufacturers sold 415.5 million rapid diagnostic tests (RDTs), with 345 million distributed through NMPs. Additionally, manufacturers supplied approximately 210 million artemisinin-based combination therapies (ACTs) to the public health sector in 2022, while NMPs distributed 217 million ACTs to the public health sector, 97% of which were distributed in sub-Saharan Africa.

Data from at least two household surveys conducted from 2005 to 2022 (baseline: 2005–2011, latest: 2015–2022) in 22 sub-Saharan African countries were analyzed to assess treatment-seeking behavior, diagnosis, and ACT use among children aged <5 years. The percentage of children treated at public health facilities increased from a median of 58 to 69%. Despite this, the utilization of community healthcare providers remained low, with a median of 2% in both the baseline and recent surveys. The median proportion of children treated in the private sector decreased from 40% in the baseline survey to 28% in the latest survey, indicating improved access to the public health sector and its associated surveillance systems. Among children aged <5 years, the diagnosis rate for those treated for fever increased from a median of 30% in the baseline survey to 54% in the latest survey, indicating improved case management despite the inadequacy of diagnostic services. The rate of ACT use among children under 5 years who required treatment rose from 13% at baseline to 24% in the latest survey. For those treated in the public health sector, the median rate of ACT use increased from 38% at baseline to 68%, suggesting either an improvement in treatment rates or an increase in test positivity among those tested.

7. Progress toward the 2020 GTS Milestones

The GTS aims to reduce the incidence and mortality rates of malaria by at least 40% by 2020, 75% by 2025, and 90% by 2030, relative to the baseline in 2015. Despite significant progress since 2000, there is a strong possibility that the GTS 2025 target will not be met globally if current trends continue. In 2022, the incidence of malaria was 58 cases per 1,000 population at risk, which was approximately 55% higher than the GTS 2025 target of 26 cases per 1,000 population at risk.

Although progress in reducing malaria mortality has been relatively better than that in reducing the incidence, the actual mortality rate in 2022 was 14.3 deaths per 100,000 population at risk in 2022, which was 53% higher than the GTS 2025 target of 6.6 deaths per 100,000 population at risk. In 2022, malaria mortality remained at the same 2015 levels in seven countries (7.5%), while it increased in 17 countries (18.3%), with eight of these countries experiencing increases of 55% or more.

8. Biological Threats to Malaria Elimination Efforts

1) Response to parasite gene deletions

P. falciparum parasites that do not express histidine-rich protein 2 (HRP2) may not be detected by RDTs designed to detect HRP2. Additionally, histidine-rich protein 3 (HRP3), a homologue of HRP2, can cross-react with monoclonal antibodies used to detect HRP2, especially at high parasite densities. Consequently, P. falciparum malaria lacking HRP2 or HRP3 expression may go undetected by HRP2-based RDTs. The WHO recommends that countries with reported Pfhrp2/3 deletions, as well as neighboring countries, establish a baseline by conducting surveys of suspected malaria cases to determine the prevalence of Pfhrp2/3 deletions that cause false-negative RDT results and assess whether it exceeds the established threshold.

In 2022, a study on Pfhrp2 deletions was conducted for the first time in six countries: Burundi, Cambodia, Cameroon, Sierra Leone, South Sudan, and Vietnam. Pfhrp2 deletions were not detected in Burundi and Vietnam. According to the Malaria Threats Map report, investigations into Pfhrp2/3 deletions have been conducted in 50 countries. The WHO response plan for Pfhrp2/3 deletions outlines several key actions, including identifying new biomarkers, improving the performance of non-HRP2 RDTs, conducting market forecasting, and strengthening laboratory networks to support the demand for molecular characterization of these gene deletions. Most P. falciparum infection cases imported into ROK come from Africa. Although there have been no reported false-negative RDT results to date, microscopic examination or genetic analysis is recommended even for negative RDT results.

2) Parasite resistance to antimalarial drugs (2015–2022)

Therapeutic efficiency studies (TES), which track both clinical and parasitological outcomes of malaria treatments, are conducted to monitor the efficacy of antimalarial drugs. Artemisinin partial resistance is assessed using the validated PfKelch13 marker, which is associated with delayed parasite clearance following treatment with artemisinin-based therapies.

In Africa, surveillance of PfKelch13 polymorphisms associated with artemisinin partial resistance has revealed evidence of such resistance associated with clonal expansion of PfKelch13 mutations in Eritrea, Rwanda, Uganda, and Tanzania. Tanzania is the fourth country in Africa to confirm artemisinin partial resistance. Additionally, an investigation into the efficacy of chloroquine (CQ) and dihydroartemisinin-piperaquine (DHA-PPQ) for malaria treatment in Ethiopia found that nine studies on CQ and two studies on DHA-PPQ reported treatment failure rates of less than 5%.

The Americas: TES conducted in Brazil (2015) and Colombia (2018) have shown that artemether-lumefantrine (AL) is highly effective against P. falciparum. Although the C580Y mutation was sporadically observed in Guyana from 2010 to 2017, recent samples have not detected this mutation, suggesting it may have disappeared. CQ is recommended as the first-line treatment for P. vivax in all malaria-endemic countries in the region, and studies in Brazil have confirmed its high efficacy.

Southeast Asia: Treatment failure rates for P. falciparum infection were below 10% in all TESs conducted during the study period. In India, treatment failure rates remained low with the use of artesunate (AS) combined with sulfadoxine-pyrimethamine. However, PfKelch13 mutations associated with artemisinin partial resistance were found at a prevalence of 65.5% in Myanmar and Thailand.

Eastern Mediterranean: The efficacy of AL for treating P. falciparum was high in Afghanistan, Pakistan, Somalia, Sudan, and Yemen from 2015 to 2020. No treatment failures were observed with P. vivax first-line drugs in the AL study conducted in Somalia (2018) or in the two CQ studies in Afghanistan (2016, 2022).

Western Pacific: Studies on the efficacy of treatments for P. falciparum have revealed high levels of treatment failure. In western Cambodia, a treatment failure rate of 13.5% with AL was reported from 2018 to 2020. Amodiaquine (AQ) resistance led to high treatment failure rates with AS-AQ in the Mondulkiri (22.6%) and Pursat (13.8%) provinces of Cambodia during 2016-2017. Additionally, high treatment failure rates with DHA-PPQ were reported in Cambodia, the Lao People's Democratic Republic, and Vietnam. As a result, Cambodia replaced DHA-PPQ with AS-mefloquine as the first-line treatment in 2016. In Vietnam, AS-pyronaridine has replaced DHA-PPQ in areas with high treatment failure rates. From 2015 to 2020, 29.9% of samples collected in Cambodia, the Lao People's Democratic Republic, and Vietnam showed PfKelch13 wild-type parasites. The PfKelch13 C580Y mutation appears to be emerging and spreading in Papua New Guinea. A 2015 study in Vietnam also reported a 9.8% treatment failure rate for P. vivax.

3) Insecticide resistance in vector mosquitoes

Since 2021, 35 countries have reported insecticide resistance data to the WHO. Globally, resistance to pyrethroids was observed in at least one malaria vector in 87% of the countries and 68% of the areas; resistance to organochlorines was reported in 82% of the countries and 64% of the areas; resistance to carbamates was noted in 69% of the countries and 34% of the areas; and resistance to organophosphates was detected in 60% of the countries and 28% of the areas. Between 2019 and 2020, WHO members reported results from 835 bioassays using chlorfenapyr and 603 bioassays using clothianidin. To date, only 13 bioassay results for clothianidin have been reported to the WHO, with only one case of possible resistance in Senegal. For resistance management, each country should develop and implement national insecticide resistance monitoring and management plans based on the WHO framework. Technical and funding support are needed to assist countries in monitoring and managing insecticide resistance.

4) Invasion and spread of Anopheles stephensi

The WHO has confirmed the presence of A. stephensi in Djibouti, Eritrea, Ethiopia, Ghana, Kenya, Nigeria, Somalia, Sri Lanka, Sudan, and Yemen. This vector mosquito is challenging to control due to its characteristics, such as ability to rapidly adapt to local environments and to withstand extremely high temperatures during the dry season, when malaria transmission typically declines. Insecticide resistance data reported to the WHO show that A. stephensi in the Arabian Peninsula and Asia has developed resistance to pyrethroids, organophosphates, carbamates, and organochlorines. In the Horn of Africa, resistance to pyrethroids, organophosphates, and carbamates has also been observed. The WHO recommends increasing vector surveillance to identify the geographical spread of A. stephensi and using this data to implement interventions aimed at preventing its further spread, particularly in urban and peri-urban areas. Countries with suspected or confirmed A. stephensi invasions should take immediate action to control this vector.

9. Climate Change, Malaria, and the Global Response

The WHO has declared climate change as the single greatest health threat facing humanity. The relationship between climate change and malaria transmission is complex, with temperature, rainfall, and humidity all influencing larval development, mosquito survival, parasite development within mosquitoes, and vector competence. Variations in these factors can affect vectorial capacity—i.e., the number of new infections a vector population would induce per case per day at a specific place and time—thereby affecting the intensity of malaria transmission. Climate change has directly impacted malaria by expanding its geographical range. Increasing temperatures over recent decades have facilitated the spread of malaria into highland areas. For instance, in 2022 and 2023, extreme monsoon rainfall in Pakistan led to a severe malaria epidemic, increasing the number of malaria cases by 5-fold compared to the number in the previous year. Despite ongoing debates about the exact direction and magnitude of climate change's impact on malaria, it is crucial for the global community to maintain and enhance sustainable and resilient malaria responses to address this evolving threat.

Malaria eradication is the only definitive solution to resolve the health burden of malaria, regardless of the added threat of climate change. Therefore, investments should focus on mitigating the biological threat of malaria and developing more effective tools. To enhance the resilience of malaria eradication efforts in the face of climate change, it is essential to significantly increase financing while also improving the use of local data for dynamic interventions at the national level. The commitment by developed countries under the United Nations Framework Convention on Climate Change to mobilize and fully operationalize the Green Climate Fund should encompass malaria and recognize the need for broader climate mitigation efforts, beyond merely reducing greenhouse gas emissions [4].

The World Malaria Report 2023 presents the latest data on global malaria elimination efforts and outcomes, focusing on information up to 2022, which marks the third year of the COVID-19 pandemic. Several important health and development objectives for malaria elimination are outlined in the Sustainable Development Goals framework [4], the WHO GTS [5], and the Roll Back Malaria partnership [6]. The GTS aims to reduce malaria case incidence and mortality by 75% by 2025 and by 90% by 2030 compared to the 2015 levels, with the goal of achieving malaria elimination in at least 20 countries by 2025 and 35 countries by 2030 [5].

Key activities for malaria control and elimination include early diagnosis with rapid diagnostic kits, appropriate treatment, vaccination, use of ITNs, and residual spraying. However, the most widely used rapid diagnostic kit may not detect infections of P. falciparum parasites lacking PfHRP-2/3 genes, and Anopheles stephensi, which has adapted to urban environments, is contributing to rising malaria cases in parts of Africa, the Middle East, and Asia. The WHO is developing guidance on managing parasite resistance to antimalarial drugs, insecticide resistance in vector mosquitoes, and cases of Plasmodium falciparum that are undetectable with current rapid diagnostic kits. This guidance underscores the need for new treatments and diagnostics. Despite these challenges, the goal of malaria eradication remains attainable, and a malaria-free future is possible through strengthened responses and accelerated research into the risks.

The Division of Vectors and Parasitic Diseases at the Korea Disease Control and Prevention Agency operates the "National Reference Laboratory for Malaria" and participates in international proficiency evaluations, such as WHO-Microscopy and UK National External Quality Assessment Services-Genetics, to ensure the reliability of test results. The division also conducts regular training and proficiency assessments for institutions responsible for confirmatory diagnosis, including public health centers and health and environment institutes located in malaria risk areas within ROK. Additionally, the division continues to share information about diagnostic technologies and malaria elimination strategies through international collaboration with the WHO, the Western Pacific Regional Office, and the Asia-Pacific Malaria Elimination Network.

Ethics Statement: Not applicable.

Funding Source: None.

Acknowledgments: None.

Conflict of Interest: The authors have no conflicts of interest to declare.

Author Contributions: Conceptualization: HIS, HIL. Formal analysis: HIS, BRK, HNJ, SDL, SYL, JWJ, JHK, HIL. Supervision: HIS, HIL. Visualization: BRK, HNJ. Writing – original draft: HIS, BRK, HNJ. Writing – review & editing: HIS, BRK, HNJ, SDL, SYL, JWJ, JHK, HIL.