Spatio‐temporal incidence of malaria patients in Incheon Metropolitan City

Malaria, a globally significant mosquito‐borne infectious disease, re‐emerged in the Republic of Korea, and manifested annually in regions close to the demilitarized zone. Notably, Incheon Metropolitan City has witnessed an alarming upswing in malaria infections in recent years, drawing attention to this public health issue. This research was conducted to catch spatio‐temporal and ecological landscape encompassing malaria patients and mosquito vectors in Incheon over the past decade. The top two incidences of malaria cases were found in Ganghwa‐gun and Seo‐gu, an occurrence potentially attributed to their geographic proximity to North Korea. Furthermore, the incidence of malaria infections displayed a seasonal pattern commencing in March, reaching its peak between June and August, and decreasing to a minimum in November. A correlation was noted between prevalence of malaria cases and number of mosquito breeding sites, such as ponds and rice fields within the region. Collectively, these research outcomes underlined the importance of systematically and holistically advocating mosquito elimination measures to enhance the efficacy of malaria eradication policies. These measures encompass the establishment of a robust mosquito outbreak surveillance system, targeted control of vector mosquitoes, residual pesticide spray, management of mosquito breeding sites, and adoption of repellents during outdoor activities.


Introduction
Malaria, a mosquito-borne infectious transmitted through biting of the infected female anopheline mosquitoes, remains a significant global health concern (Miller et al. 2002).Predominantly afflicting tropical regions, it claims more than million lives a year (WHO 2020).The Republic of Korea stands as a target for malaria eradication (E-2025) under the World Health Organization (WHO) (Wangmo et al. 2022).Recent increases in vector populations and their distribution, driven by global warming, have led to rise the incidence of vector-borne infectious diseases (Mordecai et al. 2020).Human malaria infections encompass five species, with Plasmodium falciparum and Plasmodium vivax being the most clinically significant.(Sinden & Gilles 2017).In the Republic of Korea, P. vivax has been a predominant species, with malaria cases primarily concentrated in Incheon, Gyeonggi-do, and northern Gangwon regions proximal to the demilitarized zone (DMZ) (Chang et al. 2016).Malaria was recognized as an endemic infectious disease in the Republic of Korea until 1963.Subsequently, malaria cases decreased following the initiation of malaria eradication projects.However, malaria re-emerged among soldiers stationed in the Paju area close to DMZ in 1993 (Chai 1999).This re-emergence was followed by a 38% increase in cases in 1997 compared to the prior year, with cases rising to 4142 in 2000 (Bahk et al. 2018).Korea government-initiated management project resulted in a decline in the number of cases between 2001 and 2004.However, from 2005, there were fluctuations in the number of cases (Bahk et al. 2018;Park et al. 2019).
Geographically, malaria cases were limited to the Paju area in 1994, but gradually expanded to the northern Gyeonggi area from 1995.By the year 2000, the epidemic area had extended to 17 cities and counties in Incheon Metropolitan City (MC), Gyeonggi-do, and northern Gangwon-do.Since then, malaria has persistently occurred, primarily in regions bordering DMZ in Incheon, Gyeonggi-do, and Gangwon-do (Chai 2020).
This study aimed to visualize the prevalence of malaria infections in Incheon MC, which is situated in close geographical proximity to DMZ, in order to comprehend its spatial distribution.Additionally, it sought to propose strategies for malaria elimination through analyses on spatial autocorrelation within malaria clusters.

Data source and population
A comprehensive malaria patient survey encompassed a population of 2,937,000 residents in Incheon MC (Fig. 1, Table 1).The data source for this study was the officially reported cases of malaria in Incheon MC, as documented in the records of the Korea Disease Control and Prevention Agency's integrated disease and health management system (http://is.kdca.go.kr), spanning a period from January 2013 to December 2022.This dataset was used as basic information for our investigation.These included the investigation of general patient characteristics, trends in incidence, clinical symptoms.Moreover, the study delved into epidemiological characteristics, including patient classifications and local mosquito breeding sites.This environment was identified via direct surveys of malaria patients.We employed the Pearson Correlation to analyze the relationship between malaria patient incidence and mosquito habitats frequency.

Statistical analyses
Our analytical toolkit consisted of Microsoft Excel 2016, QGIS 3.16.14, and R version 4.1.3, which were instrumental in conducting various statistical analyses (QGIS, Development Team 2015; R Core Team 2023).Furthermore, the research process entailed the verification of administrative towns, townships, and villages, complemented by calculations of resident registration central population, all of which were performed using a PC address searcher (Ministry of the Interior and Safety, database date as of March 31, 2023).Data pertaining to annual resident registration and provincial population were obtained from the National Statistics Portal.When calculating average incidence rate spanning 2020 to 2022, we cross-referenced population figures of December 2019 and December 2022 which were retrieved from the National Statistics Portal.Arithmetic means were employed to calculate an average incidence rate.

Ethics statement
This study was reviewed and approved by the Institutional Research Board of Incheon National University (approval No. 7007971-202310-001).

Malaria patients by residency, gender, and age
Over a decade, from 2013 to 2022, our study included a total of 813 malaria patients in Incheon MC (Table 2).They were 615 male and 198 female, signifying a consistent male predominance, with the number of male patients exceeding that of females by more than two-fold each year.The patients were classified into three groups: residents (727 cases), veterans (59 cases), and soldiers (27 cases), with soldiers comprising 10.5% of the total patients.There was a discernible decrease in the number of malaria patients on an annual basis, with the highest record occurring in 2015.Decrease was observed among the soldiers and veterans, which continuously decreased after 2016.
Incidence of malaria patients in an age group was highest in 20s, accounting for the highest proportion at 44.6%.This was closely followed by 60s (36%), 50s (35%), 70s (34.8%), 30s (34.1%), and 40s (31.9%) age groups (Fig. 2).Conversely, the occurrence of malaria patients was less prevalent among the elders in their 90s (14.7%), teenagers (13.6%), and children under 10-year-old (6.1%).The high incidence of malaria in the 20s age group was presumed to be influenced by the presence of soldiers and veterans stationed at military in Ganghwa-gun, which is situated in close proximity to North Korea in which residents had a notable malaria burden.
Incidence rate of malaria per 100,000 residents exhibited substantial regional variations, with Ganghwa-gun recording the highest rate at 300 cases per 100,000 people (Table 3) followed by Ongjin-gun 64 cases, Jung-gu 47 cases, and Seo-gu 41 cases.The incidence rate in other areas, including Yeonsu-gu, Gyeyang-gu, Dong-gu, Michuhol-gu, Bupyeong-gu, Bupyeong-gu, and Namdong-gu, ranged 12-24 cases per 100,000 people.On average, Incheon MC had a population of approximately 293,700 residents by region (Table 1).Notably, Ganghwa-gun, Ongjin-gun, and Jung-gu, despite having populations lower than the city average, exhibited a higher incidence rate per 100,000 individuals compared to other regions.Conversely, Bupyeong-gu and Namdong-gu reported a lower incidence rate per 100,000 residents relative to their population (Table 3).

Symptoms of the patients
Fever and chills were the most common symptoms observed in malaria patients in Incheon MC, with approximately 80% of the patients reporting these symptoms.Headaches, sweating, and muscle pain were prevalent, appearing in about 50% of the cases, while dizziness and vomiting were less frequently reported (Table 4).An analysis of major symptoms by age group revealed that fever (20.5%) and chill (20.6%) were most frequently observed in individuals in their 50s.For those in their 20s, sweating (22.0%), headache (24.5%), dizziness (32.9%), and vomiting (23.1%) were the predominant symptoms.Muscle pain was present in around  3).
Examining the temporal trends in malaria cases in Incheon MC, it was evident that the number of cases surged by 56.0% to 131 in 2014.Subsequently, from 2016 to 2019, the incidence stabilized at 80-87 cases annually.However, in 2020-2021, the number of cases almost halved.In 2022, there   3).Malaria infections exhibited a distinct seasonal pattern over the course of a year in Incheon MC.Case reports of the infections typically commenced in March, rapidly increased, and reached a peak in August.Subsequently, there was a sharp decline, with the lowest number of infections occurring in November.An intensive malaria transmission was occurred between June and September (Fig. 3).In Ganghwa-gun, the highest number of infections was reported in July, and from April to October, these months collectively accounted for over 50% of the total monthly infections.On the other hand, in Ongjin-gun, a notable increase in the number of infections was observed in August, with patients being discovered in December as well, indicating a distinctive outbreak pattern (Fig. 3).

Incidence of malaria patients and mosquito breeding sites
Regarding the mosquito breeding environment in the residential areas of malaria-infected patients within Incheon MC, a substantial proportion of patients, approximately 46.3%, reported the presence of mosquitoes in their residences and workplaces.Additionally, 151 patients (11.1%) reported presence of rice fields around their homes, while 25 patients (1.8%) noted existence of a nearby reservoir.Furthermore, 87 patients (6.4%) reported presence of waterways, 52 patients (3.8%) mentioned wetlands, 33 patients (2.4%) cited streams, 201 patients (14.8%) identified hilly areas behind their residences, and 179 patients (13.2%) recognized bushy areas (Fig. 4).The data implied that environments conducive to mosquito occurrence and habitat were prevalent in the residential areas of malaria-infected individuals.A notable correlation coefficient of 0.881 was calculated between malaria infection and the mosquito breeding environment, underscoring that the likelihood of malaria infections was substantially higher in regions where mosquito habitats were reported within residential areas.

Discussion
Malaria cases in Republic of Korea exhibited a concentration in regions proximal to the DMZ (Ree 2000).It is well-documented that malaria has been endemic in North Korea since the 1990s and continues to be a concern (Chang et al. 2016).Indeed, the movement of mosquito vectors across the DMZ was a concern and could contribute to the transmission of malaria between North and Republic of Korea.This is an important consideration for public health authorities in the region, as it can influence occurrence of malaria infections in areas near the DMZ (Shin et al. 2008).The unique environmental attributes of the DMZ, marked by diverse wetland-like vegetation, potentially create an environment conducive to mosquito breeding, thus contributing to the observed concentration of malaria cases (Lefevre et al. 2013).Furthermore, the influence of climate and environmental factors in the northern region of Incheon MC should be considered, as these variables have been shown to affect malaria transmission (Paaijmans et al. 2010;Arab et al. 2014).Climatic parameters such as temperature and humidity, particularly during the period from June to August, foster heightened mosquito activity, thereby increasing the likelihood of malaria transmission and infection (Li et al. 2013).Indeed, the climatic conditions can significantly impact mosquito activity and, consequently, the potential of malaria transmission and infection (Shin et al. 2008).Of significant note is the confirmation that Ganghwa-gun stands out as the highest incidence of malaria cases in Incheon MC (Kim et al. 2021).Various regional factors, including topography, aquatic features, land utilization, and outdoor human activities, are instrumental in shaping the distinct characteristics of malaria incidence (Pope et al. 2005;Vanwambeke et al. 2007;Moshi et al. 2018;Fornace et al. 2021).The close proximity of Ganghwa-gun to North Korea increased potential of geographical influences on the local epidemiology of malaria transmission (Han et al. 2006;Sriwichai et al. 2017;Kim et al. 2019).Vivax malaria has been endemic in North Korea for the past three decades, with the highest infection rates recorded among residents near the DMZ (Kim et al. 2019).In the region south to the DMZ, Anopheles kleini was a predominant mosquito species  carrying malaria parasites.This species exhibited correlation between monthly frequency of malaria infection cases and monthly number of malaria parasite-positive mosquitoes.Furthermore, within a 2 km range from the DMZ, both number of P. vivax-positive mosquitoes and malaria-infected people was significantly higher compared to areas located 11-12 km away (Chang et al. 2016;Kim et al. 2019).It was also important to acknowledge that Anopheles mosquitoes have been found to be capable of traveling long distances when taking wind currents, potentially introducing mosquito vectors from overseas.This potential should not be overlooked in this context (Huestis et al. 2019).
Our analyses revealed a distinct pattern, with malaria cases commencing in March, increasing from June to August, and subsequently declining by November, underscoring the seasonality to malaria transmission.Ganghwa-gun emerged as an epicenter of this seasonal fluctuation, with over 50% of malaria cases occurring there from April to October.An alignment of this trend with the global pattern of increased malaria transmission during the summer season underscores the importance of this particular hotspot.(Han et al. 2023).Moreover, our study exposed an anomalous phenomenon in Ongjin-gun, where malaria cases persist beyond the typical summer transmission season, even extending into December.The P. vivax malaria parasite prevalent on the Korean Peninsula, including North Korea, displayed a combination of short-term and long-term incubation forms (Shin et al. 2008).The occurrence of malaria patients in the winter, a period when vector mosquitoes are absent, is seemed to be attributed to infections with long-latent P. vivax form (Shin et al. 2008).
Recent reports suggested that the mosquito microbiome can exert an influence on malaria transmission (Gendrin et al. 2015;Romoli & Gendrin 2018;Gao et al. 2020;Vinayagam et al. 2023).Additionally, differences in the microbiome of Anopheles mosquitoes between regions with frequent malaria cases in the northern area and areas with rare malaria occurrences have been noted in Republic of Korea (Lee et al. 2023).Indeed, the microbiome of mosquitoes in the Incheon MC area exhibited a similar pattern to regions with frequent malaria cases, hinting at a potential relationship between the occurrence of malaria patients in Incheon MC and the mosquito microbiome (Lee et al. 2023).To provide a more accurate understanding of this relationship, further investigations are warranted to determine whether Anopheles mosquitoes in the Incheon MC area carry malaria parasites and to explore their microbiome.Such research could contribute to more comprehensive understanding of the factors driving malaria transmission in the region.
The seasonal trends observed in malaria incidence in Incheon MC, marked by unique geographical and temporal variations, underscore the imperative need for adaptive control measures, in alignment with previous findings (Buckee et al. 2017).Our study results offer crucial ecological insights for crafting malaria control strategies in the Incheon MC.Given the concentration of malaria infections in Incheon's northern region, particularly areas proximate to the DMZ, it is imperative to employ highly focused control measures that consider ecological factors and environmental conditions (Castro 2017).A pest control strategy tailored to the unique circumstances of each county or district should be devised and implemented, encompassing both mosquito larval control and adult control mobilizing local resources.Preemptive measures to manage mosquito vector habitats are essential.From April to October, these habitats, including rice paddies, reservoirs, waterways, wetlands, streams, and mountain forests, which have been identified as relevant in the epidemiological investigation of malaria cases, should undergo intensive quarantine and disinfection.This approach is crucial for effectively curtailing occurrence of the malaria-carrying mosquitoes.The study results clearly establish a connection between the incidence of malaria infections and the quantity and distribution of mosquito habitats.Building on these findings, conducting monthly surveys to monitor mosquito production will provide a more distinct understanding of the relationship with the occurrence of malaria cases (Bertola et al. 2022).Given that Incheon MC exhibits a seasonal trend with the highest incidence of malaria infections from June to September, it is crucial to develop a mosquito control plan specifically designed for this season.This strategy should include enhanced surveillance of both mosquitoes and infected individuals, increasing the accessibility of preventive measures, and ensuring timely treatment for those who have contracted malaria disease.This focused approach aligns with the seasonal nature of malaria transmission and is essential for effective control and prevention (Shin et al. 2008).As observed in Ongjin-gun, if the incidence of infections extends beyond November, it is imperative to maintain continuous monitoring and be prepared for a sustained control activity.Malaria outbreaks require ongoing vigilance, and the count measures should be timely and well-adapted to the extended transmission period to effectively control the event.
In process to develop a malaria control plan, making data-driven decisions is paramount.Regular data collection and analysis are essential to detect emerging trends and point out high-risk areas.Data-driven decision-making is crucial for designing and implementing effective malaria control strategies (Potter et al. 2016).Establishing an early warning system for malaria outbreaks, especially in areas like Ganghwa-gun, could prove instrumental in facilitating timely interventions (Macherera & Chimbari 2016;Dhiman & Sarkar 2017;Modu et al. 2017).Even though Ganghwagun, Ongjin-gun, and Jung-gu have relatively small Spatio-temporal incidence of malaria patients in Incheon Metropolitan City Entomological Research 53 (2023) 609-617 populations, they exhibit a higher incidence rate per 100,000 people compared to other regions.Conversely, Bupyeong-gu and Namdong-gu show a lower incidence rate per 100,000 people relative to their populations.These observations underscore an approach that factors are not only the absolute number of malaria cases but also the population in project region.In addition, community participation and education are pivotal elements in the sphere of malaria control (Whittaker & Smith 2015).Such efforts should emphasize significance of personal protection measures and early diagnosis and treatment of malaria patients (Sahan et al. 2017).Health education programs should be tailored to specific characteristics of the target area, accounting for occurrence of malaria patients, seasonal fluctuations in mosquito vectors, and region-specific risk factors.Campaign of malaria prevention is of utmost importance.Instead of relying solely on traditional media, innovative methods like YouTube videos and social media news cards could be utilized for continuous education of young generations.These efforts should particularly target active-duty soldiers, given the high incidence of malaria cases in this group.

FIGURE 1
FIGURE 1 Map of malaria patient survey area in Incheon Metropolitan City.Color on scale indicate malaria patients per 100,000 people.

FIGURE 2
FIGURE 2 Annual incidence of malaria patients by age group in Incheon Metropolitan City.

FIGURE 3
FIGURE 3 Monthly incidence of malarial patients in Incheon Metropolitan City by region, 2013-2022.Regional incidence was depicted using colored line.

FIGURE
FIGURE 4 Malaria patients and breeding place of mosquitoes in Incheon Metropolitan City, 2013-2022.

Table 2
Annual incidence of malaria patients by gender and military service status in Incheon MetropolitanCity, 2013City,  -2022 revealed a concentration of cases in the northern region, with a decreasing tendency towards the southern areas (Table5).Over a past decade, Ganghwa-gun and Seo-gu, in the north and adjacent to North Korea, reported the highest number of

Table 4
Symptoms of the malaria patients in Incheon Metropolitan City, 2013-2022 0% increase, bringing the total to 63 cases.In Ganghwa-gun, the number of cases exhibited a downward trend after peaking at 32 in 2013, remaining relatively stable at approximately half that number since 2017.In the western region, the trend fluctuated with periods of increase and decrease following a peak of 38 cases in 2014.From 2017 to 2019, this region consistently reported the highest number of cases among the administrative districts in Incheon MC.Ongjin-gun reported no malaria cases in 2021 and 2022 (Table

Table 5
Regional incidence of malaria patients in Incheon Metropolitan City by year EntomologicalResearch 53 (2023) 609-617