The protozoan parasites belonging to the Plasmodium genus, which are responsible for causing malaria, reside and undergo reproduction within the erythrocytes of human hosts (Supranefly et al. 2021). According to UNICEF (2022), the four most commonly observed parasites include Plasmodium falciparum, Plasmodium vivax, Plasmodium ovale, and Plasmodium malariae. The transmission of the disease occurs through natural means, specifically when a female Anopheles mosquito engages in biting behavior. The initial symptoms commonly encountered by individuals afflicted with malaria are influenza-like symptoms, such as fever, chills, and headaches. This condition can impact individuals across all age groups. According to Supranefly et al. (2021), the symptoms of malaria often manifest within a period ranging from 10 days to 4 weeks and commonly include fever, headache, vomiting, and shivering. Throughout history, malaria has been recognized as a significant infectious illness with a profound impact on the human population. With its high rates of morbidity and mortality, the infectious disease in question has garnered significant attention from the scientific community and is a prominent issue for global health organizations (Garrido-Cardenas et al. 2019). According to the World Health Organization’s World Malaria Report of 2022, there has been a consistent decrease in global malaria fatality rates, with figures dropping from 887,000 in 2000 to 573,000 in 2015 and further reducing to 568,000 in 2019. In the year 2020, the number of deaths attributed to malaria was around 625,000, indicating a 10% increase compared to the previous year, 2019. The projected mortality figure for the year 2021 underwent a marginal decrease, resulting in a revised estimate of 619,000 fatalities. Between the years 2019 and 2021, the COVID-19 pandemic resulted in a total of 63,000 fatalities due to disruptions in critical malaria services. The World Health Organization (WHO) South-East Asia Region exhibited a secondary position, accounting for 10% of reported cases and 3% of fatalities. Conversely, the WHO Africa Region demonstrated a substantial avoidance of both cases (82%) and deaths (95%), constituting the majority in each category. The factors contributing to the increase in malaria transmission encompass the swift dissemination of quinoline-resistant malaria parasites, alterations in the environment that may facilitate the emergence of novel mosquito breeding habitats, societal instability prompting individuals to relocate to regions with elevated malaria transmission rates, and voluntary migration of non-immune populations susceptible to malaria (Dale et al. 2005). According to the World Health Organization (WHO 2020), there is a prevalent issue of malaria in 87 countries around the globe, with Indonesia being one of them. Indonesia is a prominent nation in Southeast Asia where instances of malaria are observed. In 2019, the World Health Organization (WHO) reported an estimated 658,380 cases of malaria and 1170 deaths attributed to malaria. The presence of multispecies infections and the challenges associated with identifying the specific locations of persistent transmission provide significant obstacles to the eradication of malaria in Indonesia, as well as in numerous other Southeast Asian nations. In the year 2017, it was ascertained that a majority of the districts in Indonesia had achieved the status of being free from malaria. Indonesia’s remarkable achievement can be attributed to its dispersed population, which exceeds 260 million individuals and spans over 5,000 islands. Additionally, the country’s significant internal migration, socioeconomic disparities, and decentralized governance contribute to its outstanding status. Moreover, it is worth noting that Indonesia has a rather balanced distribution of Plasmodium falciparum and Plasmodium vivax infections. Furthermore, the country harbors approximately 25 distinct species of Anopheles mosquitoes, which have developed resistance to malaria. With the exception of Bhutan and Indonesia, all nations have successfully attained the Global Technical Strategy (GTS) 2020 objective of reducing case incidence by over 40%. However, there exists a deficiency in the health system as evidenced by the persistence of high malaria transmission in the provinces of West Papua and Papua within the Papua region (Fadilah et al. 2022; UNICEF 2022). In the country of Indonesia, there exists a total of 80 distinct species of Anopheles mosquitoes that serve as vectors for the transmission of malaria. Among these species, 24 have been identified as posing a significantly elevated risk in terms of their ability to spread the illness. The distribution of these vectors, namely An. sundaicus, An. subpictus, An. barbirostris, An. maculatus, An. aconitus, and An. balabacensis, in Indonesia varies depending on the breeding location. Malaria manifests itself in various forms within the Indonesian context. The environment, encompassing physical, economical, and behavioral factors, has a significant role in enhancing the probability of malaria transmission in Indonesia (Dale et al. 2005). The growth, development, and reproduction of vectors are influenced by various physical factors, including temperature, precipitation, humidity, wind patterns, dispersed and inaccessible mosquito nesting places, and unsanitary environmental conditions. Socioeconomic factors such as nocturnal or early morning excursions, limited educational attainment, and lower middle-income status have the potential to influence the transmission of malaria. The characteristics mentioned above have been commonly associated with increased occurrences of malaria. Specifically, substandard housing circumstances and engagement in agricultural work have been identified as factors that elevate the likelihood of catching the disease (Dale et al. 2005; Lewinsca et al. 2021).

Malaria continues to pose a significant public health challenge in Indonesia, with a substantial number of individuals affected and a considerable number of deaths occurring annually. Indonesia has a substantial historical background in conducting research and development pertaining to malaria, as well as implementing strategies for the eradication of vector-borne diseases. Nevertheless, because to the intricate nature of transmission epidemiology inside this archipelago, there exists limited knowledge regarding the diverse array of mosquito species belonging to that particular type. The significance of Indonesia’s malaria research cannot be overstated in the pursuit of the ambitious goal of malaria eradication by 2030. The nation of Indonesia has a diverse and intricate epidemiology of malaria, encompassing a variety of transmission patterns, parasite species, and vectors across its numerous islands. Hence, it is imperative to do research on malaria in order to gain insights into the dynamics of the disease, advance the development and assessment of novel tools and approaches, and provide a foundation for evidence-based policies and interventions (UNICEF 2022). In the context of Indonesia, malaria research encompasses various areas, including: The field of epidemiology in relation to malaria encompasses the objectives of monitoring and assessing the trends and patterns of malaria cases and fatalities, identifying the factors that contribute to the transmission of the disease, and mapping the distribution and prevalence of malaria parasites and vectors. This approach facilitates the strategic distribution of resources, the prioritization of areas with high risk, and the customization of actions based on specific local circumstances.As an illustration, the study titled “Assessment of Malaria Risk Factors in Aceh Besar, Indonesia: Utilizing Active and Passive Surveillance Data in a LowEndemic Malaria Elimination Context with Plasmodium knowlesi, Plasmodium vivax, and Plasmodium falciparum” was conducted by Herdiana et al. in 2016. 2) The objective of malaria research in Indonesia is to enhance the precision, sensitivity, specificity, and cost-effectiveness of malaria diagnostic techniques, with a particular focus on distant and resource-constrained environments. This practice aids in guaranteeing prompt and suitable medical intervention, mitigating the occurrence of problems and fatalities, and diminishing the proliferation of medication resistance. For example, a research about evaluated the performance of a novel rapid diagnostic test (RDT) that can detect low-density Plasmodium falciparum and Plasmodium vivax infections in Mimika Regency, Papua, Indonesia (Fransisca et al. 2015). 3) Treatment: The focus of malaria research in Indonesia is to enhance the effectiveness, safety, tolerability, and adherence of malaria treatment protocols, with particular emphasis on drug-resistant strains and groups at high risk. This intervention facilitates the recovery of patients, mitigates the risk of relapses and recrudescence, and diminishes the likelihood of transmission. An illustrative study was conducted by Kenangalem et al. (2019) to assess and compare the effectiveness and safety of two artemisinin-based combination treatments (ACTs) in the treatment of uncomplicated malaria. Another area of research in malaria is focused on vector control, disease surveillance, prevention, and program management. Malaria is a significant public health challenge in developing nations such as Indonesia. According to the Indonesian Basic Health Research, there was a 6.0% increase in malaria cases in 2013 compared to 2012, with a higher prevalence observed in eastern regions of Indonesia. According to available data, a significant proportion of Indonesia’s administrative divisions, specifically 54% of its 497 districts and cities, are characterized by a high prevalence of malaria. According to Hasyim et al. (2019), it has been observed that malaria is endemic in five out of the thirty-three provinces in Indonesia, namely Sulawesi Tengah, Nusa Tenggara Timur, Maluku, Papua, and Papua Barat. The probability of contracting malaria can be heightened by many risk factors, with a notable emphasis on the availability and utilization of basic healthcare services. The dissemination of knowledge regarding malaria and the provision of aid to afflicted patients are imperative responsibilities for healthcare practitioners. Various medical facilities such as government hospitals, private hospitals, primary health services (puskesmas), clinics, midwife practices, posyandu, village health posts, and village maternity clinics can be utilized to prevent the transmission of malaria to individuals within the community. The successful eradication of malaria necessitates the implementation of basic healthcare services within the community and its associated network. This healthcare holds particular significance for individuals who are vulnerable to this illness, including pregnant women, infants, and young children (Hasyim et al. 2019).

There are several other febrile conditions, such as dengue fever, typhoid fever, the common cold, respiratory infections, dyspepsia, and pneumonia, that exhibit symptoms similar to those of malaria. This paper discusses the methodologies employed for the detection of malaria in individuals, encompassing parasitology, microscopy, and rapid diagnostic tests. Nevertheless, there are certain areas where parasitology testing is not yet available, hence posing challenges in the detection of malaria and elevating the likelihood of erroneous diagnosis and inappropriate presumptive therapy. As a consequence of these issues, individuals may inadvertently consume inappropriate antimalarial drugs due to a limited comprehension of crucial malaria symptoms and non-symptom-based criteria utilized in the clinical diagnosis of malaria. The aforementioned matter is also considered a noteworthy concern that motivates scholars to investigate prominent symptoms of malaria. The objective is to utilize these symptoms as a foundation to assist healthcare practitioners in the clinical identification of malaria and to enhance public awareness. This, in turn, enables individuals to adopt measures to protect their well-being and maintain a malaria-free environment (Bria et al. 2020).

Malaria, an infectious disease of significant global concern, presents a substantial obstacle to public health worldwide. Based on the extant records, it has been noted that this specific sickness demonstrates endemic attributes in a collective of 87 countries, including Indonesia as one of the afflicted nations. Indonesia is classified as one of the poor countries within the Association of Southeast Asian Nations (ASEAN) that demonstrates a significantly elevated prevalence of malaria. Preceding the year 2007, an estimated 80% of the nation’s rural regions and urban hubs have received official declarations of being malaria-free. According to Budiarti et al. (2020), there was a decrease in the incidence of malaria from 2.9% in 2007 to 1.9% in 2013. According to the statistics presented by the Ministry of Health of the Republic of Indonesia, it has been noticed that the region of Papua, which is known for its high prevalence and widespread occurrence of malaria, accounts for around 97% of the overall reported cases of malaria in Indonesia (Lusiyana and Ahdika 2022). According to Fadilah et al. (2022), Indonesia has become a significant area of concern for malaria within the South-East Asia region of the World Health Organization. This is evident from the estimated statistics of 784,854 cases and 1443 fatalities expected for the year 2020. Since the commencement of a malaria eradication campaign in Indonesia in 2009, there has been a sustained reduction in the prevalence of the disease in the western regions of the nation. As of the year 2020, a total of more than 300 districts and municipalities have successfully attained the designation of being free from malaria. Nevertheless, there has been a recent development stemming from the widespread occurrence of zoonotic malaria in Sumatra and Kalimantan, which correspond to the Indonesian region of Borneo (Lempang et al. 2022). The provinces of West Papua and Papua, situated in the Papua Region, are presently contending with a notable escalation in the transmission rate of the virus. Based on the findings of Fadilah et al. (2022), it was seen that in the year 2020, the two provinces under consideration were associated with approximately 90% of the reported cases on a national level. The Indonesian province of Papua has officially documented a total of 2,046,833 cases of malaria during the years 2011 and 2020. Among the overall number of reported cases, a significant majority of 1,820,566 instances (accounting for 89% of the total) were found in Papua, and the remaining 266,267 cases (representing 11% of the total) were recorded in West Papua. Plasmodium falciparum and Plasmodium vivax have been identified as responsible for approximately 90–95% of the aforementioned diseases. Fadilah et al. (2022) attributed the remaining instances to P. malariae and P. ovale. The geopolitical boundary between the Indonesian state of Sabah and the northernmost province of North Kalimantan is situated on Sebatik Island. Sebatik Island is recognized as one of the regions in Nunukan District that is endemic to malaria. Based on the findings of the Health Agency of Nunukan District (2010), there was an observed rise in the Annual Malaria Incidence (AMI) from 10.58 cases per 1000 individuals in 2008 to 12.53 cases per 1000 individuals in 2009. According to a study conducted by Sugiarto et al. (2017), it was found that in the year 2013, a total of 61 individuals out of the population of 7525 residents in Sungai Nyamuk Village tested positive for P. falciparum. The incidence rate of P. falciparum in this population was reported to be 8.11 per 1000 persons. The annual incidence of malaria parasites in North Sumatera was recorded as 0.07 in the year 2020. As of the year 2020, a total of 21 out of the 33 regencies/cities have been officially recognized as malaria-free. According to Fahmi et al. (2022), the prevalence of zero counts for P. falciparum and P. vivax was 1477 out of 1584 (93.3%) and 1387 out of 1584 (87.6%), respectively. The Asahan Regency, situated in the North Sumatra Province, exhibits a notable incidence of malaria. Nevertheless, it is anticipated that via the implementation of various strategies, the region would achieve the eradication of malaria by the year 2020, so transforming it into an area free from the burden of malaria. In a study conducted by Sembiring et al. (2020), it was noted that there was a documented rise in the incidence of malaria in Asahan District between the years 2010 and 2014, culminating in a prevalence rate of 3.38% or a total of 2,389 reported cases. Between the years 2015 and 2017, there was a notable decline in the incidence of malaria, as evidenced by a morbidity rate of 0.65% or a total of 469 reported cases. The aforementioned statistics indicate that Asahan Regency exhibits the greatest rates of morbidity compared to other districts and cities within North Sumatra Province.

Malaria is a prominent global health concern, particularly in regions with tropical climates, despite sustained international efforts to address the disease (Bria et al. 2020). Based on data provided by the Ministry of Health of the Republic of Indonesia, it is evident that Papua demonstrates a substantial prevalence and widespread distribution of malaria, as shown by an Annual Parasite Index (API) value exceeding 5 per 1000 individuals (Lusiyana and Ahdika 2022). The provinces of East Nusa

Tenggara, Central Sulawesi, Maluku, Papua, and West Papua have the highest prevalence rates of malaria. Furthermore, the provinces of Papua and West Papua, which are the largest provinces located on the island of Papua in Indonesia, exhibit an estimated annual parasite incidence (API) rate of approximately 67%. The province of Papua exhibits notable variations in air quality, as seen by the Air Pollution Index (API) indicators. The regions of Keerom, Jayapura, Timika, Sarmi, and Boven Digoel Regency stand out as the five areas with the highest API readings. According to Budiarti et al. (2020), the three districts in West Papua that demonstrate the highest API indicators are Manokwari, South Manokwari, and Wondama Bay Regency. The likelihood of recurring episodes of malaria is dependent on various variables. The aforementioned characteristics include age, gender, ethnicity, employment status, and a prior known risk factor for malaria, specifically, a familial susceptibility to the disease (Lusiyana and Andhika 2022). The increased prevalence of malaria in Papua and West Papua can be ascribed to a variety of factors. Factors contributing to the persistence of disease-causing parasites include the emergence of treatment-resistant strains, insufficient governmental initiatives, particularly in underdeveloped countries, and a dearth of healthcare infrastructure in remote areas (Budiarti et al. 2020). The province of North Sumatera is situated in the northern section of the island of Sumatra, Indonesia. Fahmi et al. (2022) assert that Medan functions as the nation’s capital and principal metropolitan hub. In terms of geographical location, it is situated at coordinates 0.589°S, 101.0°E. In the year 2016, the province of North Sumatra exhibited the greatest prevalence of malaria cases compared to other regions including the island of Sumatra. Hakim et al. (2018) reported that North Sumatra Province is positioned as the fifth province with the highest malaria prevalence among the provinces of Papua, NTT, Papua West Papua, Maluku, and North Sumatra in Indonesia. The geographical region in the eastern part of Northern Sumatera has been recognized as the focal location where both endemic and imported cases of malaria are concentrated. The eastern section of the island in North Sumatera stands out due to its coastline terrain and significant population density, distinguishing it from other regions within the province. The location of the site is characterized by the presence of wetland areas, river systems, and the Hindia ocean in its vicinity. The primary occupations in this geographical area consist of fishing and agricultural pursuits. There exists a subset of persons that demonstrate an increased vulnerability to contracting malaria, as indicated by Fahmi et al. (2022). The data can be seen in the Fig. 1.

Figure 1. 

High risk region and populations of malaria in Indonesia. (The data from the Ministry of Health, Republic of Indonesia, 2019).

Artemisinin-based Combination Therapy (ACT) is widely employed as the primary and secondary treatment strategy for malaria in numerous regions affected by the disease. The ACT regimen is composed of a synergistic blend of artemisinin or its derivatives, along with other pharmacological agents known as partner medicines, as explicated by Arya et al. in their scholarly publication of 2021. The standard first-line treatment for malaria, known as ACT (Artemisinin-based Combination Therapy), combines a powerful artemisinin derivative with a companion medicine that has a longer duration of action. Prominent instances encompass artemether–lumefantrine (CoArtem) and amodiaquine–artesunate (Coarsucam) as indicated by Ecker et al. (2012). Within the historical framework of Africa, it has been a prevailing practice to recommend a singular predominant therapeutic intervention or pharmaceutical agent for the management of uncomplicated malaria. In response to the escalating levels of drug resistance, the predominant strategy has been to substitute the existing medication with a newly developed alternative that remains unaffected by resistance. This scenario is demonstrated by the case observed in Kenya. The replacement of chloroquine with sulfadoxine-pyrimethamine as the predominant therapeutic strategy took place in the year 1998. During the time frame from 2004 to 2006, artemether-lumefantrine, an artemisinin-based combination therapy (ACT), replaced sulfadoxine-pyrimethamine as the preferred treatment option. The approach outlined above, known as the “wait-and-switch” strategy, presents significant obstacles for monitoring networks and public health systems in economically disadvantaged nations. Based on the study conducted by Boni et al. (2008), it has been shown that this specific methodology yields suboptimal outcomes in terms of both morbidity and mortality. A potentially more sustainable approach would involve the proactive utilization of presently accessible antimalarial drugs to decrease both mortality and morbidity, while concurrently delaying the emergence of resistance and the incidence of treatment failures. The global treatment of malaria cases is now guided by the World Health Organization (WHO), which recommends six various Artemisininbased Combination Therapies (ACTs). The antimalarial drug combinations that have been identified are as follows: a) the combination of artesunate and amodiaquine, b) artemether paired with lumefantrine, c) artesunate combined with sulfadoxinepyrimethamine, d) artesunate in conjunction with mefloquine, e) artesunate together with pyronaridine, and f) dihydroartemisinin jointly administered with piperaquine. The utilization of multiple artemisinin-based combination therapies (ACTs) is a fundamental aspect of the therapeutic approaches implemented by different nations facing the challenge of malaria prevalence (Arya et al. 2021). Indonesia has notably adopted a primary therapeutic strategy, utilizing artemisinin-based combination therapies (ACTs) that consist of artesunate and amodiaquine (Mutabingwa 2005).

The need of conducting follow-up assessments to determine the prevalence of susceptible strains among malaria patients is underscored by the utilization of secondline treatment for drug-resistant malaria in artemisinin-based combination therapy (ACT). The present analysis observed that all identified SNPs related to the transcription factor (TF) were shown to be linked with the artemether derivative’s companion medicine. Furthermore, a meta-analysis performed by Arya et al. (2021) unveiled that the utilization of artesunate and sulfadoxine-pyrimethamine exhibited a greater propensity for the creation of drug resistance when contrasted with lumefantrine. In contrast, it was shown that the utilization of dihydroartemisinin and piperaquine resulted in a comparatively reduced risk as compared to lumefantrine. There was no statistically significant variation detected among the different combinations of lumefantrine with artesunate and mefloquine, artesunate and amodiaquine, and artesunate and sulfadoxine-pyrimethamine. Hence, in countries where the adoption of artemisinin-based combination therapy (ACT) is lacking, a plausible approach to address the emergence of resistance to ACT may involve the utilization of dihydroartemisinin and piperaquine, as it demonstrates the lowest probability of resistance development to artemisinin-based treatments. An alternative strategy to maintain the efficacy of artemisinin-based combination therapy (ACT) would entail the intermittent utilization of alternative antimalarial medications, such as chloroquine, in areas where the efficiency of ACT has been seen to be reduced. Laufer et al. (2006) documented the reemergence of plasmodial susceptibility to chloroquine in Malawi subsequent to the discontinuation of this antimalarial medication. This finding suggests that the reintroduction of chloroquine, in conjunction with other drugs as part of artemisinin-based combination therapy (ACT), may present a promising strategy for primary treatment in these regions. Furthermore, it is important to acknowledge that the implementation of Artemisininbased Combination Therapies (ACTs), which incorporate numerous partner medications, commonly known as “triple ACTs,” has generated considerable debate. The study conducted by Arya et al. (2021) has recently examined and urged for the implementation of this alternate technique.According to a study conducted by Rahmalia et al. (2023) in Papua, a significant proportion of the study participants demonstrated a prevailing belief in the effectiveness of biomedical interventions for the management of malaria. In contrast, the utilization of traditional or herbal remedies was perceived as supplementary in nature, primarily aimed at alleviating symptoms rather than being considered a curative strategy. A wide range of nettles was administered externally to the skin, resulting in sensations of itching or heat, with the main objective of alleviating joint pain and overall physiological discomfort. It is worth mentioning that a few of persons deliberately grew these nettles in their private gardens. One particular type of nettle, known as Laportea decumana, was frequently found in local markets, where it was typically sold by vendors from highland Papuan villages. Moreover, it has been noted that bloodletting was a prevalent tradition among highland communities, utilized with the purpose of alleviating localized discomfort, such as by extracting blood from the forehead to treat migraines. The antimalaria drug action can be seen in the Table 1.

Based on the findings of the 2013 Riskesdas survey, it has been found that individuals living in urban regions, where Artemisinin-based Combination Therapy (ACT) is easily available, have somewhat higher rates of treatment compared to individuals live in rural areas, as described by Kinansi et al. in 2021. Moreover, a research conducted by Rahmalia et al. (2023) in the Papua region reveals that the mining corporation has contributed to the improvement of malaria treatment accessibility. The aforementioned improvement is demonstrated by the facilitation of complimentary healthcare services to the Kamoro and Amungme communities, as well as five other indigenous groups residing in highland areas, namely the Damal, Dani, Mee, Moni, and Nduga populations. These groups are recognized as being directly affected by mining operations. Mutabingwa (2005) highlighted notable obstacles in the acceptability and implementation of Artemisinin Combination Therapies (ACTs) in the context of malaria control. The challenges included increased expenses, higher rates of malaria transmission, a significant number of asymptomatic infections among individuals with partial immunity, improper use of pharmaceutical drugs, inadequate diagnostic infrastructure and capabilities, a lack of knowledgeable policy-makers, and weaknesses in public health systems. This study employed a comprehensive mixed-methods approach to examine the extent to which patients adhere to the radical curative treatment for Malaria. The results provide valuable insights into the important findings within the subject area. There are two key findings in Rahmalia et al.’s recent study in 2023. Firstly, ethnicity plays a significant role in determining adherence to treatment, thereby impacting its effectiveness. Secondly, individuals’ perceptions and experiences with healthcare providers from diverse backgrounds have a significant influence on treatment outcomes.

The qualitative component of Rahmalia et al.’s (2023) study sheds light on how structural factors related to ethnicity can help explain the differences in treatment adherence that are reported among various ethnic groups. The Papuan population experiences significant social and economic marginalization, resulting in limited educational and vocational opportunities compared to non-Papuan individuals. In order to address this concern, there is potential in implementing a strategy that involves community health workers who reside within the same village or neighborhood as the individuals requiring treatment. These community health workers can provide oversight and support, tailoring their visitation schedules and explanations of medication to align with the socio-ethnic background of the patients. This approach shows promise as a means of mitigating the issue at hand. Within the complex sociocultural context being examined, there exists a phenomenon wherein individuals often engage in self-diagnosis of malaria by assessing their own symptoms. In general, individuals tend to see a healthcare professional more than 24 hours after the initial appearance of symptoms. This is mostly done to validate their self-diagnosis and acquire suitable medical intervention. It is important to highlight that, similar to many other countries, Indonesia lacks a sufficient number of studies that investigate the epidemiology of febrile diseases. The implementation of point-ofcare diagnostic technologies for different etiologies of fever has the potential to improve the effectiveness of malaria control initiatives. The choice of a healthcare provider is influenced by various factors, such as familiarity, the financial costs connected with treatment and transportation, waiting times, and the perceived quality of healthcare services. Prior to seeking medical advice, patients often assess the intensity of their symptoms by self-administering therapies using leftover prescriptions from past illnesses or easily accessible over-the-counter remedies. Moreover, the application of herbal topical and oral remedies functions as supplementary approaches in mitigating symptoms, rather than acting as replacements for biological treatment modalities. Rahmalia et al. (2023) reported on the impact of supervision strategy on adherence. In the supervised arm of the investigation, qualitative investigations unveiled that both participants in the trial and the staff responsible for field supervision shared the perception that the supervised treatment schedule of alternating days was suboptimal. The participants’ reliance on face-to-face interactions with field supervision workers for the purpose of obtaining their tablets was identified as the cause of this phenomenon. If persons are not present at their residence during supervision visits, they would be unable to administer the necessary amount for that specific day.

Alongside the utilization of pesticides and malarial treatments, some adverse societal and economic factors play a role in the dissemination of malaria. The emergence of drug resistance poses a significant challenge to the eradication of malaria. It is widely recognized that the existing tools at our disposal are inadequate to attain complete eradication. Presently, the field of malaria biology relies on the use of “single-omics” methodologies in conjunction with state-of-the-art technology. Each stratum of omics data generated establishes unique associations with this pathogenic condition (Zhou et al. 2021). The advancements in “single-omics” techniques have resulted in a wide range of novel targets, including molecular markers, that can be utilized for the diagnosis of malaria. However, at present, our comprehension of the biological aspects of malaria remains insufficient. The comprehensive elucidation of all relevant molecular pathways is limited by the inherent constraints of “single-omics” methodologies, shown by the genetic variants of malaria identified through genomewide association studies (GWAS). Given the aforementioned evidence, it is imperative to employ “multi-omics” methodologies to augment our understanding of the intricate dynamics of molecular and cellular information in both Plasmodium and infected human hosts. In recent times, the field of malaria research has witnessed the effective utilization of “multi-omics” methodologies. The majority of participants endeavored to establish connections between many data levels simultaneously. Several prior studies have employed advanced computational methods to reveal previously unnoticed or undiscovered hidden structures related to “multi-omics” from highly informative information. Several studies using mosquitoes also employed “multiomics” approaches. According to Zhou et al. (2021), the utilization of “multi-omics” data has the potential to facilitate the development of novel drugs and vaccines, leading to the exploration of personalized approaches in the clinical management of malaria. This approach has promise in addressing the current challenge of drug resistance. To facilitate the advancement of novel antimalarial therapeutics, it is imperative to tackle challenges associated with drug resistance, liver stage infections, sexual plasmodial blood in individuals, transmission-blocking interventions, and relapse prevention. In 2018, the Food and Drug Administration (FDA) granted authorization for tafenoquine (TQ) as one of the newly approved drugs. In the context of avoiding relapses caused by P. vivax, the efficacy of the intervention in inhibiting heme polymerase during the blood stage surpasses that of its predecessors. The medications for malaria venture (MMV) has identified novel treatment options that show promise in terms of both product development and clinical evaluation. Natural products have been described as a valuable resource with significant potential for the advancement of medicine. Ethnopharmacology is regarded as a highly promising approach in the development of anti-malarial medications, since it serves as a valuable avenue for accessing indigenous information pertaining to herbal remedies. The antimalarial efficacy of phytochemicals derived from traditional medicine, including flavonoids, terpenoids, phenolics, coumarins, steroids, quinones, xanthones, and alkaloids, has been proven (Zhou et al. 2021). The RTS,S vaccine has emerged as the initial malaria vaccine to successfully undergo clinical trials. The presence of the circumsporozoite protein (CSP) can be observed in a recombinant fusion protein (RTS) that has been employed in this particular vaccine (Zhou et al. 2021). Presently, there are ongoing efforts to create several types of vaccines, including RTS,S vaccines like R21, as well as other anti-infective vaccines such as attenuated or irradiated whole sporozoite vaccines (PSPZ). Over the course of several decades, extensive efforts have been dedicated to the advancement of anti-infective vaccines. Notably, monoclonal antibodies have emerged as a promising class of therapeutic agents, exhibiting substantial anti-infective properties. The identification of new targets and chemistries for malaria vaccines is an ongoing requirement. However, thus far, the health advantages derived from allocating resources to clinical trials and the development of vaccines have not been deemed sufficient to warrant the associated expenses (Penny et al. 2020).

Numerous strategies have been employed in the administration of diseases transmitted by mosquitoes. However, the implementation of vector control remains a crucial component in several disease control endeavors. Throughout the course of history, the prevailing methodology for successfully eliminating malaria in diverse geographical areas worldwide has predominantly centered on the implementation of vector control measures. According to Ogunah et al. (2020), copper aceto arsenite and pyrethrum were utilized as larvicides in Brazil for the aim of pest control. The overview of Overview of vector-control tools for malaria control can be seen in Table 2.

The available literature indicates that the degree to which hospitals may effectively contribute to the improvement of primary healthcare (PHC) is highly contingent upon the particular circumstances. Nevertheless, these contributions can be broadly classified as a continuum that spans a range of activities. The activities encompass a spectrum of interventions, including the direct delivery of healthcare services and outreach initiatives that target the problem of restricted availability of high-quality primary care. Additionally, efforts are made to improve the provision and demand for frontline primary care services, such as gatekeeping and practical support. Furthermore, it is worth noting that hospitals have the potential to contribute to the advancement of integrated care, a concept that seeks to enhance the seamless and well-coordinated delivery of healthcare services to individuals (Freijser et al. 2023).Hospitals possess the capacity to function as “systems-focused hospitals” through acknowledging the interrelatedness and the necessity of engaging in collaboration with other components of the healthcare system to achieve these goals. The framework outlined in the preceding section has been constructed using an iterative approach, using pertinent scholarly sources and complemented by data gathered from a case study of a specific nation. The degree to which hospitals contribute to the improvement of primary healthcare (PHC) in different capacities is dependent on multiple factors. The elements in question cover the accessibility to primary care services at the forefront, the quality of these services, the degree of integration within the wider healthcare system, and the overall orientation of the health system, which may prioritize prevention, community-based care, or population health.

The development of innovative antimalarial medications that demonstrate strong efficiency against plasmodium parasites is currently a pressing requirement. Compounds originating from botanical sources have been exploited for therapeutic purposes since ancient times and are now included as ingredients in modern pharmaceutical formulations. A significant advantage linked to the application of chemical compounds derived from medicinal plants in the development of innovative pharmaceuticals is their considerable propensity to bind to biological receptors present in the human body. Indonesia, as a nation, harbors a diverse array of plant species that exhibit promising properties as antimalarial agents. The plant materials utilized in this study consist of the leaves of puspa (Schima wallichii Kort), senai (Wedelia bifora), and kembang bunga (Tithonia diversifolia (Hemley) A Gray), as well as the bark of cempedak (Artocarpus champeden Spreng), papaya leaves (Carica papaya), and the leaves of sambiloto (Andrographis paniculata Nees) (Alkandahri et al. 2018; Teng et al. 2019). The short summary of medicinal plant againts malaria can be seen in Table 3.

Throughout history, natural compounds have held a significant and enduring role in pharmaceutical research and development, particularly in the exploration of antimalarial drugs. Notable examples of antimalarial drugs derived from natural sources include quinine, obtained from the Cinchona plant, and artemisinin, extracted from the Artemisia plant. A study by Newman and colleagues (2016) revealed that over 60% of newly discovered antiparasitic compounds between 1981 and 2014 had their roots in natural compounds. This underscores the substantial contribution of these natural compounds to drug development. Over time, antimalarial drugs like quinine, chloroquine, amodiaquine, sulfadoxine-pyrimethamine, mefloquine, piperaquine, and halofantrine have encountered a common fate—Plasmodium parasites developing clinical resistance in specific geographic regions, leading to the spread of resistance globally (Roman et al. 2019). Presently, artemisinin derivatives, such as artesunate, artemether, and dihydroartemisinin (DHA), are the primary therapeutic drugs for malaria treatment. Both monotherapy and artemisinin combination therapies (ACT) are employed, combining artemisinin-based drugs with longer-acting antimalarials like amodiaquine, piperaquine, mefloquine, or sulfadoxine-pyrimethamine (Shah and Valecha 2016). Concerns have arisen about multidrug resistance and increased resistance to ACT, particularly in the CambodiaThailand border region (Dondorp et al. 2009). It is widely accepted in the scientific community that quinine, chloroquine, mefloquine, and amodiaquine, as well as 4substituted quinolines, share a similar mechanism of action against Plasmodium parasites. These drugs enter the parasite’s acidic digestive vacuole and disrupt the conversion of heme into non-toxic hemozoin, leading to the accumulation of toxic heme and the parasite’s demise (Egan 2008). Plasmodium parasites can develop resistance to conventional antimalarials through mutations in drug targets or changes in drug transporters (Bras and Durand 2003; Petersen et al. 2011). In the past two decades, extensive efforts have been made to develop more effective chloroquine derivatives. Modifications to the side chain, including the incorporation of various heterocyclic structures, have been successful while retaining the desired biological activity. The quinoline core, serving as the pharmacophore, has remained consistent. These modified structures, often referred to as “hybrid structures,” aim to introduce a dual mode of action that could potentially overcome resistance mechanisms (CQresistant). While many hybrid structures have demonstrated strong antiplasmodium effects against chloroquine-resistant Plasmodium falciparum, there may be limited experimental evidence to attribute the enhanced activity to a dual mechanism. Nonetheless, these innovative chloroquine analogs with functionalized side chains show promise for developing novel antimalarial drugs (Walle et al. 2020). The author’s primary goal in this context was to synthesize quinoline derivatives with a piperidine moiety in their side chains, inspired by the structural features of quinine and mefloquine. Piperidine, as a heterocyclic structure in antimalarial quinoline analogs, has been relatively understudied compared to other heterocycles like triazine, triazole, and pyrimidine. The inclusion of a piperidine moiety is believed to enhance the drug’s uptake and retention within the acidic digestive vacuole, following a mechanism similar to quinine and mefloquine. The author chose bridging and monocyclic functionalized piperidine scaffolds for conjugation with various quinoline cores. This article outlines the synthetic procedures used to create four distinct sets of novel quinoline derivatives with added piperidine side chains. These compounds were then evaluated for their antiplasmodium activity against both a chloroquinesensitive strain (NF54) and a chloroquine-resistant strain (K1) of Plasmodium falciparum, as well as their cytotoxicity in a mammalian Chinese hamster ovary (CHO) cell line (Walle et al. 2020).