The researchers searched PubMed, Google Scholar and EBSCOHost for studies published during the 10 years preceding September 2024. They included studies reporting resistance-associated point mutations in P. vivax in Southeast Asia, then extracted information on study characteristics, geographic and temporal distribution, molecular polymorphisms, and any accompanying phenotypic or clinical evidence. The synthesis followed PRISMA-ScR reporting guidance, and sampling locations were mapped at the highest spatial resolution available in each study. Of 1,560 records identified, 25 met the inclusion criteria, revealing a geographically uneven evidence base: eligible molecular surveillance studies were concentrated in six countries, with limited or no eligible data from several other Southeast Asian countries.

The clearest molecular signal involved sulfadoxine-pyrimethamine resistance. Two multilocus haplotypes were widespread across malaria-endemic areas of Cambodia, Lao PDR, Malaysia, Myanmar and Thailand: the pvdhfr F57I/L+S58R+T61M+S117N/T quadruple genotype and the pvdhps A383G+A553G double-mutant haplotype. Functional studies linked the accumulation of these antifolate-resistance genotypes to reduced drug susceptibility. In some populations, the same multilocus mutations were also associated with slower parasite clearance and a higher rate of sulfadoxine-pyrimethamine treatment failure. The review therefore places antifolate-resistance mutations ahead of the other markers examined in terms of consistency across molecular, functional and clinical evidence.

Evidence for chloroquine was less consistent. The pvcrt-o K10 insertion and several pvmdr1 polymorphisms—particularly T958M, Y976F and F1076L—were reported frequently, but their relationships with phenotypic drug susceptibility and clinical outcomes varied among studies. These polymorphisms should therefore not be treated as uniform predictors of chloroquine resistance. Similarly, mutations in pvK12 were uncommon, and the review found no validated molecular marker capable of identifying artemisinin resistance in P. vivax. Data on resistance to partner drugs used in artemisinin-based combination therapy were too limited and heterogeneous to support a comparable regional marker. The findings also emphasize that molecular detection alone cannot reliably establish the clinical significance of a resistance-associated genotype across the region.

Because this was a descriptive scoping review rather than a meta-analysis, the results summarize the distribution and consistency of available evidence rather than producing pooled effect estimates or a single comparative estimate of treatment failure. Sparse surveillance, uneven geographic coverage, and differences among studies limited the strength of cross-country conclusions. The authors called for integrated molecular, phenotypic and therapeutic surveillance to clarify how resistance-associated polymorphisms correspond to parasite susceptibility and patient outcomes. Within the evidence available through September 2024, antifolate-resistance markers in pvdhfr and pvdhps showed the strongest support, whereas chloroquine and artemisinin-based combination therapy partner-drug markers lacked consistent validation.

Subject of Research: Molecular, phenotypic and clinical evidence of Plasmodium vivax antimalarial resistance in Southeast Asia

Article Title: Unraveling antimalarial resistance in Plasmodium vivax in Southeast Asia: from molecular markers to phenotypic and clinical evidence—A scoping review

Article References: Fauziah, N., Setia Asih, P. B., Alisjahbana, B., Soetanto, I., Faridah, L., Sahiratmadja, E., Nugraha, N. F., Aviani, J. K., & Watanabe, K. (2026). Unraveling antimalarial resistance in Plasmodium vivax in Southeast Asia: from molecular markers to phenotypic and clinical evidence—A scoping review. BMC Infectious Diseases. https://doi.org/10.1186/s12879-026-14529-3

Image Credits: AI Generated

DOI: 10.1186/s12879-026-14529-3

Keywords: Plasmodium vivax, antimalarial resistance, Southeast Asia, molecular markers, chloroquine resistance, antifolate resistance, artemisinin resistance, malaria surveillance, scoping review, Unraveling, antimalarial, resistance

The study, led by Dan Jiang of the Chongqing Center for Disease Control and Prevention together with colleagues at the national institute of parasitic diseases in Shanghai, compiled every imported malaria case reported in Chongqing between 2014 and 2024. That amounted to 301 cases, with annual numbers fluctuating between 4 and 48. The predominant species was Plasmodium falciparum, the deadliest human malaria parasite, which accounted for 75.08 percent of infections, followed by P. vivax at 12.29 percent, P. ovale at 7.97 percent, and smaller numbers of P. malariae and mixed infections. Four patients developed severe malaria and three died, a reminder that even in a non-endemic setting, imported malaria remains a life-threatening condition.

The demographic profile of those infected tells a clear story about who bears the risk. Nearly 94.35 percent of cases were male, 84.71 percent were aged 21 to 50, and 60.80 percent were overseas laborers—workers, migrants and farmers employed abroad. The infections overwhelmingly traced back to Africa, with 90.37 percent of cases originating in 32 African countries; the Democratic Republic of the Congo and Nigeria each contributed 44 cases, and Guinea added 29. This pattern reflects Chongqing’s role as a key node city along China’s Belt and Road Initiative, which has expanded economic cooperation with malaria-endemic regions and sent a steady stream of young, working-age men to construction sites and enterprises in sub-Saharan Africa. Only 22 cases were recorded during the COVID-19 pandemic years of 2020 to 2022, when travel collapsed, but numbers rebounded sharply afterward, peaking at 48 in 2024—a signal that population mobility, not local ecology, drives importation.

Diagnosis often came late. The median interval from symptom onset to diagnosis was 5.6 days, and 41.20 percent of patients were only diagnosed more than a week after falling ill. The authors attribute this to low malaria awareness among returning workers and limited diagnostic capacity at county-level hospitals, where nearly half of the cases first sought care. Because falciparum malaria can progress from fever to organ failure within days, such delays carry real clinical danger, and the researchers recommend routine malaria screening for febrile patients at county hospitals, along with pre-departure education and post-arrival active screening for returning migrant workers.

But case counts alone cannot predict where transmission might restart. For malaria to re-establish locally, three conditions must coincide: imported parasites, competent vectors and environmental conditions that allow mosquitoes to survive and breed in sufficient numbers. Chongqing historically was one of China’s most malaria-burdened regions, with all of its districts and counties reporting cases—predominantly vivax malaria—before transmission was brought under control in the 1990s. No locally acquired case has been reported since 2011, and the municipality passed its national elimination assessment in 2019. The dominant vector today is Anopheles sinensis, a species found in every surveyed district between 2011 and 2025, whose larvae flourish in rice paddies, irrigation ditches, streams and marshes, and which has developed widespread resistance to pyrethroid insecticides, the backbone of standard vector control.

To map where this mosquito could persist, the team built an ensemble ecological niche model using the biomod2 framework, which integrates twelve different modeling algorithms—including random forests, gradient boosting, generalized linear models and maximum entropy—into a single consensus prediction. Occurrence records collected from 2011 to 2025 were spatially thinned so that no more than one point remained per square kilometer, yielding 127 valid records and reducing the overfitting risk from spatial autocorrelation. Environmental predictors were screened by Pearson correlation, and nine variables entered the final models, drawn from WorldClim bioclimatic data at 30-arc-second resolution and vegetation indices from NASA’s MODIS satellite product. In total, 562 individual models were fitted, each trained on 80 percent of the data and tested on the remainder, with only high-performing runs retained for the ensemble.

The ensemble model achieved an area under the receiver operating characteristic curve of 0.839 and a true skill statistic of 0.531, outperforming most individual algorithms. Among the environmental drivers, three variables dominated: bio5, the maximum temperature of the warmest month; NDVI, the normalized difference vegetation index, which captures vegetation greenness and soil moisture; and bio11, the mean temperature of the coldest quarter. These variables make biological sense. Moderate vegetation cover offers resting and egg-laying sites for adult mosquitoes, while mild winters in western Chongqing favor overwintering survival and early spring population resurgence. The resulting suitability map showed that most of Chongqing offers at least some suitable habitat, with highly suitable areas concentrated in the metropolitan core and western districts, and suitability dropping off in the high, cold mountains of the east, such as Chengkou and Wuxi.

Crucially, the researchers recognized that climatic suitability approximates only the mosquito’s fundamental niche, not its actual abundance, which depends on local factors like breeding-site availability and land use. So they overlaid field-measured vector density—captures per trap-night averaged over the June-to-October peak seasons from 2011 to 2024—onto the suitability map. The result was striking heterogeneity: the highest densities occurred in Wanzhou, followed by Yunyang, Fengjie and Fengdu, all major rice-growing areas whose extensive paddies sustain large mosquito populations, while the metropolitan districts showed uniformly low densities except in Jiulongpo. In six districts, including Beibei and Bishan, no An. sinensis were captured at all despite suitable climate, illustrating how urbanization and sustained control can suppress even a well-adapted vector.

The final step examined imported P. vivax cases specifically, because An. sinensis is the primary vector for that species in the region. Of the 39 imported vivax cases, concentrations appeared in Yubei, Hechuan and Pengshui—districts connected to international travel and labor migration, with Yubei hosting Jiangbei International Airport—and notably, 51.28 percent of these cases arrived during the peak mosquito activity season. When case importation, habitat suitability and measured vector density were all overlaid, six districts emerged as top priorities: Wanzhou, Yubei, Hechuan, Tongnan, Pengshui and Jiulongpo. Eleven more, including Tongliang, Shapingba, Jiangjin, Yongchuan, Dazu, Rongchang, Fuling, Wulong, Xiushan, Zhongxian and Wushan, were classified as moderate priority.

The framework is not without limitations, which the authors acknowledge candidly. Two historically important vectors, An. minimus and An. lesteri, were never detected in surveillance and were excluded, though they could persist at undetectable levels; the modest number of vivax cases limited quantitative risk estimation; and the district-level analysis may mask finer township-scale variation. Still, the study offers one of the first municipal-level integrations of case surveillance, niche modeling and empirical vector density in the post-elimination era, and its practical prescription is straightforward: reinforce microscopy capacity at primary clinics in high-priority districts, actively screen returning migrant workers, and concentrate seasonal vector suppression during the summer-autumn months when imported vivax cases and mosquito abundance are most likely to collide. For a city celebrating more than a decade without local transmission, the message is clear—vigilance, targeted by data, is the price of keeping malaria out for good.

Subject of Research: Integrated risk mapping of imported malaria re-establishment in Chongqing, China

Article Title: An integrated approach to prioritizing areas for imported malaria re-establishment prevention in Chongqing, China

Article References: Jiang, D., Tan, Y., Yang, M., Chen, S., Guan, H., Yang, S., Bai, H., Luo, F., Chen, J.-H., & Zhou, S. (2026). An integrated approach to prioritizing areas for imported malaria re-establishment prevention in Chongqing, China. Frontiers in Cellular and Infection Microbiology, 16, Article 1929309. https://doi.org/10.3389/fcimb.2026.1929309

Image Credits: AI Generated

DOI: 10.3389/fcimb.2026.1929309

Keywords: imported malaria, malaria re-establishment, Anopheles sinensis, ecological niche modeling, biomod2, Chongqing, Plasmodium vivax, Plasmodium falciparum, vector surveillance, spatial epidemiology, China, malaria elimination

The team, led by Sampreeti Tahbildar and Ashis Das of the Molecular Parasitology and Systems Biology Lab at BITS Pilani, published their findings in Frontiers in Malaria on 11 November 2025. Their approach relied on array-based comparative genomic hybridization, a technique that measures the relative abundance of every segment of a parasite genome by competitively hybridizing fluorescently labeled test and reference DNA onto a dense microarray. Rather than sequencing whole genomes, which can struggle with the repetitive, GC-rich regions that litter malaria parasite chromosomes, the researchers designed a custom 2 × 400K tiling array carrying 418,577 oligonucleotide probes spaced an average of just 56 base pairs apart across the entire P. vivax genome. That density, anchored to the P. vivax Sal-1 reference genome, allowed them to detect copy number changes as small as 100 base pairs and as large as nearly 1.5 megabases.

The clinical material came from patients admitted to S.P. Medical College in Bikaner, in northwestern India, a region where P. vivax remains endemic. Blood samples were drawn after informed consent, processed within fifteen minutes of collection, and confirmed as pure P. vivax infections using microscopy, rapid diagnostic tests, and an 18S rRNA gene-based multiplex PCR that ruled out P. falciparum co-infection. Three isolates came from patients with cerebral malaria, defined by a Glasgow coma scale score below 11, and three came from patients with uncomplicated disease. Genomic DNA from each group was pooled, labeled with distinct fluorescent dyes, and hybridized against each other on the tiling array. CNVs were called using the ADM-2 algorithm, a standard tool in Agilent array-CGH analysis, with stringent filters requiring at least three consecutive probes showing an average absolute log2 ratio of 0.3 or greater, a threshold designed to eliminate single-probe artifacts arising from sequence mismatches.

The results were striking in their breadth. Copy number variations appeared across all 14 chromosomes of the P. vivax genome, affecting a total of 2,138 genes. Altered intervals ranged from roughly 100 base pairs to approximately 1,429 kilobases. The single most extensive CNV spanned about 1,450 kilobases on chromosome 12, covering 316 genes in a continuous stretch of amplification. Chromosome 14 and chromosome 10 also carried large amplified blocks, encompassing 100 and 96 genes respectively. Many of the affected genes encode hypothetical proteins whose functions remain uncharacterized, a reflection of the persistent difficulty in maintaining P. vivax in continuous laboratory culture, which has hampered functional studies of the parasite for decades.

Among the most consequential findings were CNVs in genes linked to antimalarial drug resistance. The team detected amplifications in three genes encoding putative multidrug resistance proteins belonging to ABC transporter families, including PVX_097025, PVX_080100, and PVX_118100. Amplification of the P. falciparum ortholog of PVX_080100 has previously been associated with mefloquine resistance, and increased copy number of the multidrug resistance gene 1, mdr1, has been repeatedly linked to elevated drug tolerance in both P. falciparum and P. vivax. Earlier work by Suwanarusk and colleagues showed that pvmdr1 amplification in Thai P. vivax isolates correlated with higher IC50 values for mefloquine and artesunate, providing functional evidence that copy number changes at this locus translate into measurable drug resistance phenotypes. The current study also identified amplification of a putative chloroquine resistance marker protein on chromosome 12 and deletion of a putative chloroquine resistance transporter on chromosome 1, echoing field observations from the Brazilian Amazon where multi-copy pvcrt-o has been tied to chloroquine treatment failure.

Equally significant were the CNVs detected in genes encoding surface antigens, the molecular interface between parasite and host immune system. All 24 tryptophan-rich antigens, or TRAgs, showing copy number changes were amplified, consistent with the tendency of this gene family to proliferate through duplication and diversification. One amplified TRAg, encoded by PVX_088850, is known to interact with PvMSP7 at the merozoite surface, suggesting a role in stabilizing protein complexes required for red blood cell invasion. The study also found copy number changes in 23 genes encoding serine-repeat antigens, all clustered on chromosome 4, with 19 in deleted regions and four in amplified regions. Amplifications were detected in genes for reticulocyte-binding proteins, or PvRBPs, which mediate invasion of young red blood cells, and in genes for rhoptry proteins, early transcribed membrane proteins, and cytoadherence-linked asexual proteins located on chromosomes 7 and 14. In P. falciparum, CLAG proteins are known to drive cytoadherence, the process by which infected erythrocytes bind to host endothelial cells, and to form nutrient uptake channels at the host cell membrane.

Perhaps the most intriguing signal came from the vir gene family, a large subtelomeric multigene superfamily unique to P. vivax. The analysis identified CNVs in 117 unique vir genes, with 84 located in amplified regions, 10 in deleted regions, and 23 showing both gains and losses. Vir genes have been proposed to mediate cytoadherence of infected red blood cells to host endothelial cells, a process that can obstruct microvasculature and contribute to tissue damage, and their extensive sequence diversity is thought to facilitate antigenic variation, allowing the parasite to stay one step ahead of host immunity. Amplification of vir genes in cerebral malaria isolates could, in principle, enhance both immune evasion and the adhesive phenotypes implicated in severe disease, though the authors are careful to note that this remains a hypothesis requiring functional validation.

Beyond coding regions, the study detected CNVs in intergenic stretches of the P. vivax genome, a finding that may carry regulatory implications. Intergenic regions harbor promoters, enhancers, and insulators that govern the expression of neighboring genes, and copy number changes in these non-coding sequences can alter the accessibility of regulatory elements to transcription factors or disrupt long-range chromatin interactions. In P. falciparum, intergenic regions are known to give rise to regulatory long non-coding RNAs that influence gene expression, sexual development, and parasite transmission. In humans, non-coding CNVs have been shown to modify gene regulation and phenotypic outcomes. By analogy, intergenic CNVs in P. vivax could reshape the regulatory landscape of genes encoding surface antigens, drug resistance proteins, and stress-related factors, though the authors emphasize that experimental studies are needed to confirm any such role.

The study also documented copy number changes in genes encoding components of the ubiquitin-proteasome system, with 20 genes from the ubiquitin machinery and 9 from the proteasomal degradation pathway showing CNVs. The proteasome serves as the primary engine of protein degradation in Plasmodium, and ubiquitylation levels rise during the transition from intracellular schizont to extracellular merozoite stages. Ubiquitin modification has also been associated with altered parasite susceptibility to multiple antimalarials, making these CNVs potentially relevant to treatment outcomes. Additional amplifications were detected in 12 genes encoding PHIST proteins, which in P. falciparum participate in host cell remodeling and have been differentially expressed in cerebral and pregnancy-associated malaria, as well as in approximately 80 genes encoding ribosomal complex proteins and in the gene for plasmepsin IV, an aspartic protease involved in hemoglobin digestion within the parasite food vacuole.

The authors are candid about the limitations of their work. All samples came from a single location, Bikaner, and were collected between 2007 and 2008, which may constrain the generalizability of the observed CNV patterns. The small sample size, three cerebral malaria isolates and three uncomplicated controls, reflects the practical difficulty of recruiting severe P. vivax cases, which remain comparatively rare relative to uncomplicated infections. The pooled design provides a group-level overview rather than individual-level resolution, and the authors explicitly state that they cannot conclude whether the observed CNVs contribute directly to disease severity. What they can say is that these copy number changes were present in cerebral malaria isolates when compared with uncomplicated cases, and that they cluster in genes and regions with plausible roles in immune evasion, drug resistance, cytoadherence, and host-pathogen interaction. To their knowledge, no previous whole-genome CNV analysis has been performed on P. vivax cerebral malaria isolates, making this a foundational dataset for future investigations. The microarray data have been deposited in the NCBI Gene Expression Omnibus under accession number GSE288219, allowing other groups to interrogate the findings independently. As P. vivax continues to shed its reputation as a benign parasite, studies like this one point toward a future where genomic surveillance of copy number variation could identify biomarkers for severe disease and inform more effective strategies for malaria control and treatment.

Subject of Research: Copy number variation analysis of Plasmodium vivax isolates from cerebral and uncomplicated malaria cases in India

Article Title: Genomic dynamics of clinical Plasmodium vivax: comparative genomic hybridization in severe malaria cases

Article References: Tahbildar, S., Boopathi, P. A., Kochar, S. K., Kochar, D. K., Aiyaz, M., Mugasimangalam, R. C., Rao, S. N., & Das, A. (2025). Genomic dynamics of clinical Plasmodium vivax: comparative genomic hybridization in severe malaria cases. Frontiers in Malaria, 3, Article 1667330. https://doi.org/10.3389/fmala.2025.1667330

Image Credits: AI Generated

DOI: 10.3389/fmala.2025.1667330

Keywords: Plasmodium vivax, copy number variation, cerebral malaria, comparative genomic hybridization, drug resistance, surface antigens, vir genes, intergenic regions, India, malaria severity, microarray, genomics

The socioeconomic dimension of malaria looms large in the editorial’s framing. Although profound knowledge exists in targeted prevention, treatment, and detection, people in endemic countries often have limited access to these services. In 2020, people in low- and middle-income countries spent 40 percent of their income on healthcare, a burden that risks pushing households deeper into poverty. Malaria is also shaped by social inequities such as low education, agricultural work, and unprotected housing, all of which increase human exposure to infected mosquitoes. The authors argue that these structural vulnerabilities demand coordinated global approaches rather than fragmented, country-by-country responses, particularly as climate change, wars, and economic decline continue to erode hard-won gains.

Accurate measurement of the disease burden underpins every elimination strategy, and several contributions in the Research Topic address this need directly. Drawing on data from the 2021 Global Burden of Disease database, Zhou and colleagues assessed malaria in the Comoros across indicators including incidence, prevalence, mortality, disability-adjusted life years, years of life lost, and years lived with disability. Their analysis showed that the malaria burden in the Comoros decreased between 1999 and 2021, driven mainly by epidemiological changes. Yet the study also revealed persistent hotspots of vulnerability: women under 40, school-aged children, and adults under 30 continue to carry a higher malaria burden than other groups, signaling where interventions should be concentrated.

In low-transmission settings, conventional case counts lose sensitivity, and serological surveillance offers a way forward. Lubis and colleagues conducted a cross-sectional study in 2019 in Langkat District, North Sumatra Province, Indonesia, where malaria incidence has declined significantly but low-level transmission persists. The team measured antibody responses to two blood-stage antigens of Plasmodium falciparum and Plasmodium vivax: merozoite surface protein-1 (MSP-1) and apical membrane antigen 1 (AMA-1). Seroprevalence for P. falciparum reached 10.6 percent for PfAMA-1 and 13 percent for PfMSP-1(19), while seroconversion rates were 18.6 percent for PvAMA-1 and 7.4 percent for PvMSP-1(19). The authors concluded that this serological assay is suitable for identifying epidemiological risk factors and supporting surveillance where elimination programs must be triggered by the earliest signals of residual transmission.

Blocking transmission from asymptomatic carriers is another critical frontier. Mmasi and colleagues used a direct membrane feeding assay (DMFA) with blood from gametocytemic participants to test how three variables influence infection of female Anopheles gambiae sensu stricto mosquitoes: artemether-lumefantrine (AL) treatment, mosquito feeding time during day versus night, and serum replacement. Infection rates in mosquitoes declined after AL treatment and were unaffected by whether mosquitoes fed during the day or at night, but rates increased after serum replacement. These findings, the authors note, will pave the way for optimizing the DMFA as a standardized tool for evaluating transmission-blocking interventions, a key step toward interrupting the silent chain of asymptomatic gametocytemia that sustains malaria in endemic regions.

Modeling studies in the Research Topic extend these insights to policy decisions. Seong and colleagues built a dynamic transmission model for P. vivax in the Republic of Korea and adapted it with demographic and climate data from the Democratic People’s Republic of Korea (DPRK), then evaluated the impact of tafenoquine administration and rapid diagnostic tests (RDTs) on malaria incidence from 2014 to 2018. The results are striking: a 1-day RDT would reduce malaria incidence by over 65 percent over the next decade, while a single-dose regimen of tafenoquine, compared with the standard 14-day regimen of primaquine, would prevent 77.5 percent of relapses and 11.3 percent of malaria cases. The combination of tafenoquine and RDTs, the authors conclude, appears to be a convincing strategy for eliminating P. vivax as a major public health problem in the DPRK, where the relapsing nature of the parasite makes diagnosis and radical cure especially challenging.

Imported cases pose a different kind of threat to elimination programs. Saudi Arabia established a malaria elimination program years ago, yet a study by Alghamdi and colleagues in Jeddah City between 2018 and 2023 documented 2,124 imported malaria cases, underscoring the need for novel antimalarial prevention protocols. Jeddah’s role as a global logistical hub for tourism through its air- and seaports makes it particularly exposed. Nearly 50 percent of the imported cases originated from Pakistan, and more than 30 percent came from African countries. Parasitologically, 38 percent of cases were caused by P. falciparum, the species responsible for most malaria deaths, while 57 percent were P. vivax infections. The findings illustrate how international travel and trade can reintroduce parasites into malaria-free areas, demanding vigilant screening at points of entry.

The COVID-19 pandemic’s disruption of malaria services in Africa between 2000 and 2022 provided the backdrop for another investigation. Amegatcher and colleagues implemented a community health education and medical screening (CHEMS) approach in Southern Ghana, conducting a cross-sectional survey in Accra and the Central regions that enrolled 953 people. Of these, 136 participants underwent both a malaria prick test and a COVID-19 nasal swab, with both samples analyzed by PCR. The results showed that 6 percent of participants were infected with malaria against a background of SARS-CoV-2 infection rates ranging from 12 to 37 percent, and notably, 2 percent were coinfected with both malaria and COVID-19. The study demonstrates how integrated community screening can simultaneously address two overlapping epidemics and maintain malaria surveillance during health system shocks.

Insecticide resistance emerged as the second major focus of the Research Topic, with at least four articles dedicated to the problem. Machange and colleagues evaluated a new combination net, ProNetDuo, which pairs bifenthrin, a fluorinated pyrethroid related to permethrin, with chlorfenapyr, an inhibitor of cellular energy production. In experimental hut trials at M’be in Cote d’Ivoire and Lupiro in Tanzania, using 18 huts with free-flying wild mosquitoes, the team compared ProNetDuo against Interceptor G2 nets, which contain alpha-cypermethrin and chlorfenapyr and have proven efficacy in malaria reduction. Using two endpoints, 72-hour mosquito mortality and the proportion of mosquitoes that successfully blood-fed, the researchers found that ProNetDuo showed inferior mortality but was superior in preventing blood feeding. The authors conclude that ProNetDuo, with its bifenthrin component, offers a valuable alternative against pyrethroid-resistant Anopheles gambiae populations.

Even the best nets fail if people do not use them. Savi and colleagues modeled urban malaria dynamics in Accra, Ghana, incorporating demographic and epidemiological factors, and identified limited living space and bed-net repurposing as critical barriers to reducing malaria prevalence. They recommend one-on-one sensitization campaigns to understand why adoption of insecticide-treated nets lags in urban and slum settings. In Ethiopia’s Shebella Bernata District, Minwuyelet and colleagues found that bed-net use among pregnant women was significantly associated with antenatal care attendance, educational status, and exposure to informative messages, yet only 45.1 percent of pregnant women used insecticide-treated bednets, well below WHO standards. A literature review by the same authors covering 61 research articles published between 2011 and 2015 confirmed severe resistance to pyrethroids and organochlorines in the principal African vectors, Anopheles gambiae sensu lato and the Anopheles funestus group, while highlighting three candidate insecticides with retained susceptibility: clothianidin, a neonicotinoid; chlorfenapyr, a pyrrole; and broflanilide, a meta-diamide.

The editorial closes with a sober warning. Beyond the scientific progress documented across the Research Topic, reductions in international donor funding from the US administration and other stakeholders since 2025 threaten to undermine all achievements, a scenario recently modeled for tuberculosis with substantial impacts on mortality and morbidity. The authors emphasize that modern scientific tools exist in abundance, but only careful observation, coordinated responses, strong quality assurance systems, and sustained investment, particularly for vulnerable groups such as children and pregnant women in rural areas, will convert these tools into elimination. One contribution also addresses the threat of invasive vector species, documenting the spread of a malaria-transmitting Anopheles mosquito into a previously malaria-free area west of Johannesburg, while six contributions illustrate the necessity of novel monitoring mechanisms to detect infections early in areas of low transmission. The message is clear: the tools are ready, but the funding and political will to deploy them remain the decisive variables.

Subject of Research: New tools and strategies for addressing contemporary threats to global malaria control, including insecticide resistance, invasive vectors, drug efficacy, and surveillance in low-transmission settings

Article Title: Editorial: Addressing contemporary threats to global malaria control: new tools and strategies

Article References: Kaiser, A. E., Messenger, L. A., Oxborough, R., & Matowo, N. S. (2026). Editorial: Addressing contemporary threats to global malaria control: new tools and strategies. Frontiers in Malaria, 4, Article 1776838. https://doi.org/10.3389/fmala.2026.1776838

Image Credits: AI Generated

DOI: 10.3389/fmala.2026.1776838

Keywords: malaria, insecticide resistance, Anopheles gambiae, insecticide-treated nets, tafenoquine, rapid diagnostic tests, Plasmodium vivax, Plasmodium falciparum, seroprevalence, transmission blocking, global malaria elimination, vector control

The shift in perception is more than academic. As malaria elimination programs push into regions where P. vivax dominates, the parasite’s ability to relapse and its capacity to cause severe complications threaten to undermine hard-won gains. The articles gathered in this Research Topic highlight the complex interplay among parasite biology, host genetics, and treatment approaches, emphasizing that managing vivax malaria goes far beyond simply clearing the parasite from the bloodstream. It requires accounting for host genetic factors that determine whether a treatment will be safe and effective for a given patient.

One of the thorniest problems in vivax malaria control is achieving a safe and effective radical cure. Primaquine, currently the only widely available 8-aminoquinoline drug, is the sole licensed agent capable of eliminating dormant liver-stage hypnozoites, the forms of the parasite that lie in wait and trigger relapses weeks or months after an initial infection. But primaquine’s use is complicated by host genetic factors, most notably glucose-6-phosphate dehydrogenase (G6PD) deficiency and variations in drug metabolism. G6PD is an enzyme that protects red blood cells from oxidative damage, and individuals with deficient variants can suffer acute hemolysis when exposed to oxidative stress from the drug.

A clinical trial included in the Research Topic assessed low-dose primaquine given alongside artemether-lumefantrine or dihydroartemisinin-piperaquine in the Solomon Islands. While both combinations reduced recurrent parasitemia compared to treatments without primaquine, neither achieved optimal radical cure efficacy. These results suggest that currently recommended lower-dose regimens may not be sufficient in areas where relapsing parasite strains are common, and they underscore the need for optimized dosing strategies that balance effectiveness against safety. Poor adherence to the conventional 14-day primaquine regimen further compounds the problem, contributing to treatment failure and recurrent infections, while regional variations in parasite responses to antimalarial therapies reflect differences in parasite genetic diversity, drug susceptibility, and transmission intensity.

In this context, tafenoquine warrants parallel consideration alongside primaquine as an alternative short-course anti-relapse therapy. Its single-dose regimen may help overcome the adherence barriers associated with prolonged primaquine treatment. However, tafenoquine is not a universal replacement for primaquine. It carries important limitations, including the absolute requirement for reliable quantitative G6PD testing before administration, contraindications or restricted use in individuals with significant G6PD deficiency, and the need for careful patient selection and safety monitoring. The choice of radical cure, the editorial argues, should therefore be individualized according to the patient’s G6PD status, regional parasite characteristics, local drug availability, and the realistic likelihood of adherence.

The significance of these safety concerns is brought into sharp relief by a case report of primaquine-induced hemoglobinuria in a G6PD-deficient patient with the Mahidol variant from Bangladesh. The case demonstrates the potentially severe outcomes of administering primaquine without prior G6PD screening, resulting in acute severe hemolysis that required blood transfusion. The report emphasizes the practical value of point-of-care G6PD testing and genetic screening in malaria-endemic areas. As global malaria programs improve access to radical cure, incorporating reliable G6PD diagnostics into everyday clinical practice will be crucial in minimizing adverse outcomes while ensuring effective relapse prevention.

Beyond treatment challenges, understanding the biological basis of severe vivax malaria remains essential. A genomic study by Tahbildar and colleagues offers new insights into parasite factors that may be linked to disease severity. Using a high-resolution comparative genomic hybridization platform, the researchers identified extensive copy number variations (CNVs) across all 14 chromosomes of P. vivax isolates obtained from cerebral malaria cases, in comparison to uncomplicated infections. These genomic changes affected genes involved in erythrocyte invasion, immune evasion, cytoadherence, and antimalarial drug resistance, suggesting that structural genomic variation might play a role in parasite adaptation and virulence.

Notably, the study detected amplifications in multidrug resistance-associated genes, reticulocyte-binding proteins, merozoite surface proteins, and virulence-associated vir gene families, pointing to potential mechanisms that may enhance parasite adaptability and pathogenicity. Importantly, the analysis also revealed CNVs within intergenic regions, raising the possibility that regulatory genomic elements contribute to parasite fitness and disease outcomes. Although the limited sample size precludes definitive causal inferences, these findings represent a pioneering effort to characterize structural genomic variation in severe P. vivax malaria and provide a valuable basis for identifying biomarkers of severe disease and understanding the evolutionary factors underlying parasite pathogenicity.

Taken together, the studies in this Research Topic reinforce several key points. Severe vivax malaria is a real clinical condition shaped by multiple factors affecting both host and parasite biology. Managing the disease effectively requires considering host genetic factors that influence treatment safety and effectiveness, not just parasite clearance. And advancements in molecular epidemiology and genomics are deepening our understanding of parasite diversity, potentially enabling better diagnostic, prognostic, and therapeutic tools. The combination of clinical medicine, pharmacogenomics, and parasite genomics showcased here reflects the multidisciplinary approach needed to tackle the evolving challenges presented by P. vivax.

As malaria elimination efforts progress, the ongoing issues of relapsing infections, emerging drug resistance, and severe clinical forms could threaten control gains. Future research, the editorial concludes, should focus on integrating genomic surveillance, enhancing point-of-care diagnostics, personalizing radical cure approaches, and conducting long-term clinical studies to better identify the factors that contribute to severe disease and treatment outcomes. These priorities are vital for creating safer and more effective strategies for malaria control and elimination worldwide.

Subject of Research: Severe vivax malaria

Article Title: Editorial: Global perspectives on severe vivax malaria: incidence, outcomes, and biological mechanisms

Article References: Kochar, D. K. (2026). Editorial: Global perspectives on severe vivax malaria: incidence, outcomes, and biological mechanisms. Frontiers in Malaria, 4, Article 1923808. https://doi.org/10.3389/fmala.2026.1923808

Image Credits: AI Generated

DOI: 10.3389/fmala.2026.1923808

Keywords: Plasmodium vivax, severe malaria, cerebral malaria, primaquine, tafenoquine, G6PD deficiency, radical cure, hypnozoites, copy number variation, parasite genomics, malaria elimination, antimalarial drug resistance

The central promise of malaria molecular surveillance is deceptively simple: read the parasite’s genome and you can read the epidemic. Genetic data can reveal whether infections are imported or locally acquired, how transmission clusters shift across space and time, and whether drug-resistant lineages are quietly expanding. High-throughput sequencing, increasingly complemented by targeted and portable platforms, now makes it feasible to genotype parasites at the scale programs require, while a maturing analytical toolkit converts raw sequence data into epidemiologically meaningful signals. Yet the editors are candid about persistent obstacles: methods must be accessible, appropriately matched to the question at hand, and able to deliver actionable information to the program officers who need it.

A recurring barrier has been the cost, infrastructure, and specialist expertise that next-generation sequencing demands, which are often unavailable precisely where surveillance is most needed. Several contributions tackle this head-on by validating targeted approaches that recover information comparable to whole genome sequencing at a fraction of the cost. Niaré and colleagues present a highly multiplexed molecular inversion probe panel for Plasmodium falciparum that targets common single-nucleotide polymorphisms and approximates whole-genome-based assessments of selection and relatedness, effectively bringing genome-scale inference within reach of programmatic budgets. In a complementary evaluation, Cabrera-Sosa and colleagues benchmark newly developed SNP barcode panels for both P. falciparum and P. vivax against established microsatellite markers in the Peruvian Amazon, offering evidence-based recommendations for panel selection in endemic settings.

Accessibility extends beyond cost savings to physical location. Adegbola and colleagues applied portable Oxford Nanopore sequencing to characterize drug-resistance loci within an antenatal-care population in Nigeria, demonstrating how decentralized platforms can lower the barrier to in-country genotyping and embed genomic analysis in routine clinical touchpoints. The technical significance is considerable: nanopore sequencers are compact, relatively inexpensive, and can operate outside well-resourced reference laboratories, meaning that resistance profiling no longer depends on shipping samples across continents. On the vector side, Boddé and colleagues demonstrate improved species assignment across the entire Anopheles genus using a targeted-sequencing assay for mosquito genotyping paired with updated reference databases, a critical advance given that accurate vector identification underpins every entomological intervention from bed nets to larval source management.

The second theme of the collection is translation: turning genomic data into programmatically actionable outputs that resolve transmission dynamics and parasite connectivity. Pereus and colleagues evaluated P. falciparum diversity across mainland Tanzania using genetic metrics of complexity of infection, parasite connectivity, and transmission intensity, revealing heterogeneity that conventional indicators such as case counts and prevalence surveys can miss. In malaria-endemic regions, transmission is often intensely focal, with hotspots and residual pockets persisting even as overall burden falls, and genomic signatures can pinpoint these pockets with a resolution that routine surveillance cannot match.

That sensitivity to changing dynamics is equally valuable for Plasmodium vivax, the stubborn relapsing parasite that poses unique elimination challenges. Fola and colleagues used population genetic metrics to track P. vivax transmission indicators through a period of transmission decline and subsequent rebound in two endemic areas of Papua New Guinea, showing that genomic signals can capture changing transmission dynamics precisely where they are hardest to measure by conventional means. As countries push toward elimination and case numbers dwindle, traditional metrics lose statistical power; genetic relatedness among the few remaining infections becomes one of the few reliable signals of whether transmission is truly interrupted or quietly continuing.

Perhaps the most consequential use case is antimalarial drug resistance, which remains one of the greatest threats to malaria control globally. Kattenberg and colleagues used genetic surveillance to document the spread of artemisinin-combination-therapy resistance during a period of malaria decline in Vietnam between 2018 and 2020, producing outputs with immediate implications for treatment guidelines and containment efforts. The finding illustrates the operational value of molecular surveillance: when resistance genotypes are mapped in near real time, national programs can adjust first-line therapies, target containment measures to affected regions, and anticipate further spread before it overwhelms treatment policy. The Oxford Nanopore-based profiling of crt, dhfr, and dhps resistance markers in pregnant women reported by Adegbola and colleagues points toward new approaches for embedding resistance genotyping into existing clinical infrastructure such as antenatal care, where pregnant women already receive routine screening and treatment.

Yet real gaps remain between capability and routine use. Safarpour and colleagues synthesized the challenge for one critical elimination use case: distinguishing imported from locally acquired infections. They found that current methods are still limited by cost, by an inability to reliably discriminate between imported and local parasites, by difficulties tracking parasite movement across borders and at within-country or smaller spatial scales, and by reliance on cross-sectional summary statistics that capture only snapshots of transmission rather than its continuous evolution. Their review also highlights a persistent neglect of P. vivax and other non-falciparum species. While P. falciparum accounts for the major burden of global malaria cases, eradication will require concerted efforts to address the unique biology of the relapsing, dormant-liver-stage parasites that characterize vivax malaria.

Encouragingly, several contributions reflect expanding sequencing and bioinformatics capacity, along with growing scientific leadership, within malaria-endemic regions themselves. Investments in regional sequencing hubs, local expertise, and collaborative research networks are enabling countries to generate and interpret genomic data relevant to their own public health priorities rather than exporting samples and analysis abroad. The editors stress that this momentum must be sustained if molecular surveillance is to become routine public health practice rather than remain constrained to research. The next phase, they argue, should focus on generating fit-for-purpose data at the scale and timeliness necessary for translation into decision-making, which will require sustained investment in local infrastructure, harmonized and tailored analytical frameworks, and closer engagement between genomic scientists and national programs.

The editors also emphasize that the future of malaria genomics lies in integration: combining parasite and vector data, and layering molecular, epidemiological, clinical, and environmental information into a coherent picture of transmission. As national programs confront evolving biological and operational challenges, from drug resistance to climate-driven shifts in vector ranges, genetic data will play an increasingly central role in guiding interventions, informing policy, and sustaining progress toward elimination. The collection stands as both a technical benchmark and a roadmap, showing that the tools for genome-informed malaria elimination largely exist, and that the decisive work ahead is making them routine, equitable, and fast enough for the programs that depend on them.

Subject of Research: Malaria molecular surveillance and genomics

Article Title: Editorial: Advanced genetic and genomic methods and applications for malaria surveillance

Article References: Ruybal-Pesántez, S., Kattenberg, J. H., Ghansah, A., & Auburn, S. (2026). Editorial: Advanced genetic and genomic methods and applications for malaria surveillance. Frontiers in Genetics, 17, Article 2000967. https://doi.org/10.3389/fgene.2026.2000967

Image Credits: AI Generated

DOI: 10.3389/fgene.2026.2000967

Keywords: malaria, genomics, molecular surveillance, drug resistance, Plasmodium falciparum, Plasmodium vivax, Anopheles, public health, Editorial, Advanced, genetic, genomic

The clinical backdrop is essential to understanding why follow-up matters at all. Plasmodium vivax is the more widespread of the two malaria parasites that still circulate in Cambodia, and it poses a unique treatment challenge. Unlike its deadlier cousin Plasmodium falciparum, P. vivax can hide in the liver as dormant forms called hypnozoites, reawakening weeks or months later to cause relapsing infections. The only widely available drug capable of clearing these dormant stages is primaquine, a medication that comes with a serious caveat: in patients with a deficiency of the enzyme glucose-6-phosphate dehydrogenase, or G6PD, primaquine can trigger potentially dangerous destruction of red blood cells. Ensuring that patients adhere to the full course of treatment, and monitoring them for adverse effects, is therefore a cornerstone of safe vivax case management. Without follow-up, health systems have no way of knowing whether patients finished their pills or whether the drug caused harm.

Recognizing this gap, Cambodia’s National Center for Parasitology, Entomology and Malaria Control tasked village malaria workers in 2021 with supporting health facility workers in conducting patient follow-up. VMWs are lay community members, typically elected or nominated by their own villages and trained to diagnose malaria with rapid tests and dispense basic treatment. Over the last two decades they have been credited with helping drive down malaria transmission in Cambodia’s most inaccessible areas, where health facilities may be hours away by foot or motorbike. Extending their role from diagnosis and treatment into post-treatment follow-up was a logical step, but one whose real-world implementation had never been systematically evaluated. The research team, led by Sarah A. Cassidy-Seyoum of the Menzies School of Health Research and Maastricht University, set out to fill that void.

The study’s design combined the numerical with the narrative. On the quantitative side, the researchers analyzed patient-specific surveillance data from nine study sites covering the period from January 2021 to March 2023, complemented by national aggregate figures. On the qualitative side, they conducted interviews and focus group discussions with a broad sweep of actors: national policymakers, sub-national program officials, health facility workers, village malaria workers, and patients themselves. The qualitative material was subjected to thematic analysis, and the two data streams were then interpreted together through an interpretivist theoretical framework of implementation science, drawing on concepts such as expectation, coherence, adoption, and a component of feasibility the authors call ‘doability’. This framework, which blends elements of existing implementation models, allowed the team to ask not just whether follow-up happened, but how the people doing it understood and shaped the intervention.

The headline numbers tell a story of rapid improvement. In 2021 and 2022 combined, 2,138 patients with P. vivax malaria received primaquine across the study sites. Of these, 39 percent were followed up in 2021, the first year of the policy. By 2022, that figure had climbed to 88 percent, a striking jump that suggests the system found its footing quickly. More than half of all follow-up contacts took place at the community level, meaning that village malaria workers, rather than facility-based staff, were carrying the bulk of the burden. For a program that relies on volunteers embedded in remote villages, this distribution is exactly what policymakers would have hoped for: the care reaching patients where they live, rather than requiring patients to travel for a check they might otherwise skip.

But the qualitative findings are where the study earns its keep, because they reveal that the uniform policy produced far from uniform practice. The researchers found that the way and extent to which follow-up was implemented varied considerably depending on the strategies individual VMWs adopted to make the intervention workable in their own circumstances. Some workers showed flexibility on which days patients were visited, adjusting schedules around farming seasons, festivals, or the patient’s own availability rather than rigidly adhering to a fixed timetable. Others reached patients indirectly through their family members when the patients themselves were away from home, using household networks as a proxy for direct contact. These were not deviations from the spirit of the policy so much as pragmatic adaptations to its letter, allowing VMWs to fulfill the intervention’s core purpose of enhancing adherence and treatment safety even when strict protocol compliance was impractical.

What emerged from the interviews was a picture of community health workers who had internalized not only the stated purpose of follow-up but also additional value they attributed to it. Beyond checking on medication adherence and watching for adverse effects, VMWs described comforting patients during an illness that can be frightening and debilitating, and conducting informal health education during their visits, teaching households about malaria prevention and the importance of completing treatment. In other words, the follow-up visit became more than a pharmacovigilance checkpoint; it became a touchpoint for broader community health engagement. The authors argue that this added value, alongside the adaptive strategies that made the intervention doable, explains why follow-up became so well embedded in the VMWs’ existing roles and responsibilities rather than being experienced as an unwelcome burden.

The theoretical framing matters here for what it implies about health policy more broadly. Implementation research has long grappled with the gap between how interventions are designed on paper and how they are enacted in practice, and the Cambodian follow-up program offers a vivid case study. The interpretivist lens used by the researchers treats VMWs not as passive conduits of policy but as active agents who interpret the intervention, negotiate its demands, and creatively solve the problems it presents. The study’s conclusion leans into this insight: rather than trying to standardize away the variation, the authors recommend that these adaptive strategies be integrated into policy and existing infrastructure, while encouraging and resourcing the kind of grassroots problem-solving that remains grounded in formal guidelines and training. The goal is to preserve both the intervention’s intended purpose and the added value that workers themselves bring to it.

The implications extend well beyond Cambodia’s borders. Plasmodium vivax remains one of the most stubborn obstacles to malaria elimination across the Asia-Pacific and the Americas precisely because of its relapsing liver stages, and radical cure with primaquine, increasingly guided by G6PD testing, is central to elimination strategies. Any such strategy depends on patients actually completing treatment and being monitored for safety, which in turn depends on health systems reaching people far from clinics. Community health workers are the backbone of that reach in dozens of countries, and the Cambodian experience suggests that their success hinges on factors that spreadsheets rarely capture: trust, flexibility, family networks, and a sense of ownership over the intervention’s purpose. For program designers, the message is that feasibility is not a fixed property of an intervention but something that frontline workers actively construct, visit by visit and patient by patient.

The study, funded by the Australian National Health and Medical Research Council and conducted in collaboration with Cambodia’s national malaria control program and its implementation partners, arrives at a moment when the Greater Mekong subregion is pushing hard toward malaria elimination. Cambodia has made remarkable strides, but the last mile is notoriously the hardest, and vivax malaria is the parasite most likely to stand in the way. By documenting both the measurable scale-up of follow-up coverage and the human ingenuity that made it possible, this research provides a template for other endemic countries considering similar community-based models. It also serves as a reminder that in global health, the distance between a policy document and a cured patient is often bridged by a village worker with a motorbike, a flexible schedule, and a clear sense of why the work matters.

Subject of Research: Implementation of community health worker follow-up for Plasmodium vivax malaria case management in Cambodia

Article Title: Community patient follow-up as a part of P. vivax case management in Cambodia: a mixed methods study

Article References: Cassidy-Seyoum, S. A., Chheng, K., Chanpheakdey, P., Meershoek, A., Hsiang, M. S., von Seidlein, L., Adhikari, B., Tripura, R., Ley, B., Price, R. N., Lek, D., Thriemer, K., & Engel, N. (2026). Community patient follow-up as a part of P. vivax case management in Cambodia: a mixed methods study. BMC Health Services Research. https://doi.org/10.1186/s12913-026-15274-8

Image Credits: AI Generated

DOI: 10.1186/s12913-026-15274-8

Keywords: malaria, Plasmodium vivax, Cambodia, community health workers, village malaria workers, primaquine, treatment adherence, implementation research, pharmacovigilance, health services research, malaria elimination, patient follow-up

The challenge the researchers set out to address is familiar to every elimination program. As transmission falls, infected individuals increasingly carry very small numbers of parasites in their blood, often below the threshold that a microscopist examining a blood smear can reliably detect. These submicroscopic infections still contribute to onward transmission, because mosquitoes that feed on an infected person can pick up gametocytes even when the density of parasites in the peripheral blood is tiny. In settings such as the Amazon basin, where P. vivax in particular hides in the liver and re-emerges in relapses, missing these infections allows reservoirs of disease to persist in communities that appear, on paper, to be approaching elimination.

Loop-mediated isothermal amplification was developed as a molecular diagnostic that avoids the thermal cycling equipment required by conventional PCR. Instead of repeatedly heating and cooling a sample, LAMP uses a strand-displacing DNA polymerase and four to six specially designed primers that recognize six to eight distinct regions of the target genome. The reaction proceeds at a constant temperature, typically around 60 to 65 degrees Celsius, which can be maintained by a simple heating block or even a water bath. Amplification produces enormous quantities of pyrophosphate and protons as byproducts, and in a colorimetric formulation a pH-sensitive dye shifts color when the reaction succeeds, turning a positive result into something a technician can read with the naked eye.

That simplicity is what makes cLAMP attractive for field surveillance, but the technology has a well-known Achilles heel: sample preparation. DNA extraction remains the most technically demanding and contamination-prone step in any molecular assay, and the choice of extraction method can dominate overall performance. The Peruvian team confronted this directly by comparing two approaches on the same samples. The first was a mini spin column method, in which DNA is bound to a silica membrane, washed, and eluted in clean buffer, a process that concentrates and purifies genetic material but requires more reagents, equipment, and hands-on time. The second was a boil-and-spin method, in which a small piece of dried blood is simply heated in water or buffer to release DNA, then briefly centrifuged to pellet debris, leaving crude lysate ready for amplification.

The samples came from two complementary surveillance strategies that elimination programs run in parallel. Active case detection, abbreviated ACD, involves health workers visiting communities and screening people regardless of whether they feel ill, in order to flush out asymptomatic carriers. Passive case detection, or PCD, relies on patients who come to a clinic with fever or other symptoms. The study analyzed 574 dried blood spots from active detection and 431 from passive detection. Dried blood spots themselves are a surveillance workhorse: a finger-prick of blood spotted onto filter paper, dried, and stored, they are cheap to collect, stable at ambient temperatures for weeks to months, and far easier to transport from remote river communities to a laboratory than whole blood or slides.

To judge how well cLAMP performed, the researchers benchmarked it against two references. Real-time quantitative PCR, or qPCR, served as the molecular gold standard, while microscopy represented the current reality of most field diagnosis. The gap between the two was stark. In the active detection set, qPCR identified 125 positive samples, 117 of them P. vivax and 8 P. falciparum. Microscopy, run against that standard, achieved a sensitivity of only 57.6 percent, meaning it missed more than four in ten infections that were genuinely present. cLAMP with the crude boil-and-spin extraction did somewhat better, reaching 63.2 percent sensitivity, while cLAMP paired with the spin column extraction climbed to 82.4 percent, a dramatic improvement over the smear.

The passive detection samples told a related but distinct story. Here qPCR found 140 positives, comprising 129 P. vivax infections, 9 P. falciparum infections, and 2 mixed infections containing both species. Because symptomatic patients generally carry higher parasite densities, microscopy fared better in this group, achieving 72.9 percent sensitivity. cLAMP with boil-and-spin extraction reached 77.1 percent, roughly comparable to the smear, while the column-based extraction again pushed sensitivity to 82.1 percent. Across both surveillance modes and all diagnostic methods, specificity remained above 99 percent, indicating that false positives were vanishingly rare and that a positive result could be trusted as a true infection.

The pattern in these numbers carries a clear technical message. The amplification chemistry itself is sensitive enough, but its real-world performance is gated by the quality of the DNA template fed into it. Boil-and-spin extraction releases parasite DNA but also carries blood-derived inhibitors and leaves the template dilute, which hurts most precisely where sensitivity matters most: in the low-density, often asymptomatic infections found by active case detection. Column-based extraction cleans and concentrates the template, and the benefit shows up disproportionately in the ACD samples, where cLAMP with columns outperformed microscopy by nearly 25 percentage points. In passive surveillance, where parasite densities run higher, the extraction method mattered less because even crude lysate contained enough template for the reaction to succeed.

For program managers weighing options in low-transmission settings, the study frames a trade-off rather than a single verdict. Boil-and-spin cLAMP is cheaper, faster, and simpler, and it performs at least as well as microscopy, making it a plausible upgrade for laboratories that cannot sustain column-based workflows. Column-based cLAMP, meanwhile, delivers sensitivity approaching qPCR from a filter paper sample, without needing a thermocycler or fluorescent detection hardware, and it substantially outperforms the smear in exactly the active surveillance campaigns where finding hidden infections is the whole point. Because the readout is a visible color change, results do not require expensive instruments, and the isothermal reaction can run on basic laboratory equipment already common in regional health posts.

The authors conclude that cLAMP, particularly when combined with column-based DNA extraction, is a practical and sensitive complementary tool for malaria surveillance in elimination settings. As countries in the Amazon and beyond push toward the last mile of malaria elimination, the infections that matter are the ones nobody can see under a microscope, and tools that can find them cheaply, reliably, and close to the communities where they occur will determine whether the final stretch of the campaign succeeds. This study suggests that a color-changing tube, a filter paper spot, and a careful choice of extraction chemistry may be enough to bring molecular-grade detection out of the reference laboratory and into the field.

Subject of Research: Evaluation of colorimetric loop-mediated isothermal amplification for malaria detection from dried blood spots in the Peruvian Amazon

Article Title: Detection of Plasmodium vivax and Plasmodium falciparum using colorimetric loop-mediated isothermal amplification from dried blood spots collected in active and passive malaria surveillance in the Peruvian Amazon

Article References: Nolasco, O., Gómez, J., Rodríguez-Ferrucci, H., Gamboa, D., & Delgado-Ratto, C. (2026). Detection of Plasmodium vivax and Plasmodium falciparum using colorimetric loop-mediated isothermal amplification from dried blood spots collected in active and passive malaria surveillance in the Peruvian Amazon. PLOS Neglected Tropical Diseases, 20(10), e0014366. https://doi.org/10.1371/journal.pntd.0014366

Image Credits: AI Generated

DOI: 10.1371/journal.pntd.0014366

Keywords: malaria, Plasmodium vivax, Plasmodium falciparum, LAMP, colorimetric assay, dried blood spots, molecular diagnostics, active case detection, passive case detection, Peruvian Amazon, malaria elimination, DNA extraction

The scale of the problem the researchers are targeting is enormous. According to estimates by the World Health Organization, malaria was responsible for approximately 600,000 deaths in 2024, and Célia Regina da Silva Garcia, a professor in the Department of Clinical and Toxicological Analysis at FCF-USP, notes that an estimated 90 percent of those deaths are caused by P. falciparum. Effective treatments for malaria do exist, but the parasite has progressively developed resistance to frontline drugs such as chloroquine and artemisinin, the backbone of current therapy in most endemic regions. That erosion of drug efficacy has made the search for new chemical classes of antimalarials a global priority, and it is precisely the gap that the São Paulo team’s work is designed to fill.

The strategy the researchers pursued is known as drug repurposing, an approach that has gained traction across infectious disease research because it exploits compounds whose pharmacology, safety profiles, and synthetic routes are already partly understood. Rather than screening millions of novel chemicals, repurposing starts with molecules validated for another indication and asks whether they also act against a new target organism. In this case, the team synthesized and tested fourteen derivatives of an antineoplastic, or cancer-treating, drug against P. falciparum parasites cultured in the laboratory. The in vitro experiments were funded by the São Paulo Research Foundation (FAPESP) through a series of research grants and fellowships supporting the laboratory’s long-running program on parasite cell biology and chemotherapy.

The results were striking in two respects. First, the molecules proved effective at killing the parasite during its asexual stage, the phase in which Plasmodium invades and reproduces inside human red blood cells and produces the cyclical fevers that define clinical malaria. A drug that clears asexual parasites is, by definition, a treatment: it addresses the disease in the symptomatic patient. Second, and arguably more important from a public health perspective, the compounds also acted against gametocytes, the specialized sexual-stage parasites that are taken up by Anopheles mosquitoes during a blood meal and that make onward transmission possible. A therapy that eliminates gametocytes would not only cure the individual patient but could also block the passage of the parasite from humans back into the mosquito vector, interrupting transmission chains at the community level.

This dual-stage activity is rare among antimalarial candidates. Most existing drugs are optimized for the blood-stage parasites and have little or no effect on mature gametocytes, which is one reason malaria transmission can persist even in treated populations. A single molecule class capable of both curing the patient and reducing infectivity to mosquitoes would be a valuable addition to the therapeutic arsenal, particularly in regions pursuing malaria elimination rather than mere control. The São Paulo findings, while still confined to laboratory cultures, indicate that the 6-anilinopurine scaffold underlying these compounds deserves serious attention as a platform for exactly that kind of transmission-blocking chemotherapy.

Underlying the antiparasitic effect, the researchers believe, is a specific molecular target inside the parasite’s cell: histone deacetylase enzymes, and in particular an enzyme known as PfHDAC1. Histone deacetylases regulate gene expression by modifying the proteins around which DNA is wound, and they have long been recognized as important drug targets in cancer chemotherapy, which helps explain why compounds designed as anticancer agents would show activity against a parasite. By inhibiting the parasite’s version of the enzyme, the derivatives appear to disrupt essential developmental programs in Plasmodium. Garcia explains that the team’s experiments have strengthened the hypothesis that histone deacetylase enzymes are an important therapeutic target for malaria, and that this understanding has allowed the group to design new molecules that are increasingly potent and selective against the parasite.

That structure-activity analysis is the second major contribution of the study. The fourteen tested derivatives varied in their chemical structure, and by comparing how those structural differences changed antiparasitic potency, selectivity, and target engagement, the team gathered the information needed for rational drug design. As Garcia describes it, rational design allows chemists to refine a molecule’s structure in a targeted manner rather than relying on trial and error. In practical terms, the researchers can now adjust side chains and functional groups to maximize inhibition of the parasite enzyme while minimizing interaction with human cells, a balancing act that determines whether a laboratory hit can ever become a safe medicine.

Safety, in fact, remains the central caveat. Because the work so far has been conducted entirely in vitro, the potential side effects of the compounds in patients have not yet been assessed. Some of the tested derivatives showed reduced efficacy against human cells while retaining their effect on the parasites, an encouraging sign of selectivity that suggests a lower risk of serious adverse effects. Nevertheless, Garcia is candid about the concerns: molecules in that class can cause fatigue, nausea, vomiting, and hematological changes such as a decrease in platelets, and she acknowledges that it is natural for such concerns to exist. Only in vivo tests, in animal models and eventually in clinical trials, can confirm whether the therapeutic window observed in culture dishes holds up in a living body.

There is also a pharmacological hurdle specific to this chemical class that the team must overcome. Drugs of this type tend to degrade rapidly inside the body, which can undermine their effectiveness regardless of how potent they are in a test tube. In vivo studies will therefore serve a second purpose beyond safety: verifying whether the candidate molecules remain chemically stable long enough in a patient’s circulation to reach and clear the parasite. Stability, selectivity, and potency together form the triad of criteria that any successor compound emerging from the group’s rational design program will need to satisfy before it can advance toward preclinical and clinical development.

Looking further ahead, Garcia’s team intends to extend its testing to other malaria-causing parasite species, most notably Plasmodium vivax, which is the predominant malaria parasite in Brazil and across much of the equatorial world. P. vivax poses distinct challenges: it can cause relapses even after treatment because it produces latent liver-stage forms called hypnozoites that can reactivate months later, and it is more widespread in equatorial countries than P. falciparum. Garcia emphasizes that evaluating antimalarial drug candidates against different parasite species is essential to ensure they are effective in the various regions of the world where malaria burden is concentrated. If the 6-anilinopurine derivatives, or the optimized molecules designed from them, prove active against multiple Plasmodium species and safe enough for human use, the cancer research toolbox may yet deliver one of the most sought-after prizes in tropical medicine: a single therapy that treats the sick and stops the spread.

Subject of Research: Repurposing anticancer 6-anilinopurine derivatives as dual-stage antimalarial compounds targeting Plasmodium falciparum histone deacetylase

Article Title: Anti-cancer molecules show promise in the fight against malaria

Article References: Anti-cancer molecules show promise in the fight against malaria. (n.d.). Original publication

Image Credits: AI Generated

DOI: Not provided

Keywords: malaria, Plasmodium falciparum, drug repurposing, anticancer compounds, histone deacetylase, gametocytes, University of São Paulo, FAPESP, ACS Omega, drug resistance, Plasmodium vivax, rational drug design

A research team led by Nicholas J. Arisco, Pablo S. Fontoura, Cassio Peterka, and Marcia C. Castro examined 5,521,411 de-identified malaria cases recorded between 2003 and 2023 in the national Sivep-Malaria surveillance system, covering 808 municipalities across all nine states of the Brazilian Amazon. Their central question was deceptively simple: when malaria disappears from a locality, how often does it come back, and where does the returning parasite come from? The answer, they found, is that imported infections are far more consequential than raw case counts suggest, and that the geography of parasite movement has shifted dramatically in recent years.

Overall, 959,281 cases, or 17.38 percent of the total, were classified as imported, meaning the infection was acquired somewhere other than where it was reported. The overwhelming majority of cases, 81.68 percent, were caused by Plasmodium vivax, with Plasmodium falciparum accounting for 17.15 percent. Crucially, falciparum malaria, the species responsible for the most severe and deadly infections, was disproportionately common among imported rather than locally acquired cases, meaning that travelers were effectively ferrying the most dangerous parasite across municipal borders.

To make sense of two decades of movement, the team turned to multivariable monthly sequence analysis, a technique borrowed from social science that treats each municipality’s year-by-year pattern of local and imported cases as a sequence to be clustered. This produced five distinct Municipal Malaria Importation Trajectories, ranging from municipalities on the verge of elimination to areas with sustained high local transmission, along with two intermediate profiles characterized by declining transmission accompanied by either intense or moderate levels of importation. The clustering revealed that the path toward elimination is not a single road: localities with similar case counts can face very different risks depending on whether they sit at the end of a parasite importation pipeline or serve as sources exporting infections to their neighbors.

The researchers then built mobility networks separately for each parasite species and for different locality types, including rural areas, urban centers, government-planned settlements, indigenous villages, and mining sites. This parasite-specific lens exposed a striking temporal shift. After mid-2020, the structure of case exportation changed markedly, and by 2023 more than half of all exported cases originated in mining localities, even though such areas cover only about 0.2 percent of the land in the region. Illegal and informal gold mining camps, which draw mobile, largely unregistered workforces deep into forested terrain, have become the engines of parasite dispersal.

The overlap between mining and indigenous territories emerged as a particular flashpoint. Falciparum importation became increasingly concentrated in municipalities overlapping the Yanomami Indigenous Land, a vast territory in the northern Amazon that has faced a well-documented humanitarian and health crisis fueled by illegal mining. The study’s findings place quantitative weight behind what health authorities have long observed anecdotally: the confluence of mining activity and indigenous communities creates corridors through which parasites penetrate some of the most vulnerable and least-served populations in Brazil.

Perhaps the most sobering results concern what happens after malaria returns to a locality that had eliminated it. Using a rule-based classification procedure tailored to each parasite species, the team identified cases of reintroduction, defined as locally acquired infections occurring after at least three consecutive years of zero local transmission. Between 2006 and 2023, they documented 63 such reintroduction events for falciparum malaria and 221 for vivax. Reintroduction did not remain a single spark: in 6 municipalities for falciparum and 23 for vivax, the returning parasite reestablished sustained local transmission, ultimately generating 864 subsequent falciparum cases and 6,524 subsequent vivax cases.

The persistence of these outbreaks is what worries elimination strategists most. Once malaria regained a foothold, transmission continued for an average of 762 days for falciparum and 815 days for vivax, meaning that a single reintroduction event could undo years of progress and burn through public health resources for more than two years before being brought back under control. Vivax poses an added biological challenge, because its parasites can lie dormant in the liver and relapse weeks or months later, silently sustaining a chain of transmission that is difficult to detect and interrupt without radical cure treatment.

The spatial pattern of reintroduction follows Brazil’s so-called arc of deforestation, the crescent of agricultural frontier, logging, and settlement that sweeps across the southern and eastern Amazon. These are precisely the municipalities with high receptivity, meaning the ecological conditions, abundant vectors, and susceptible populations that allow malaria to flourish once introduced. As Brazil pushes toward elimination, the set of receptive municipalities with zero local transmission grows, and each imported infection in such a place carries the potential to restart transmission from scratch.

The authors argue that the path forward requires mobility-informed surveillance and targeted reactive strategies rather than uniform, geography-blind interventions. In practice, that means using importation trajectories to identify which municipalities nearing elimination are most at risk, concentrating resources on the mining-indigenous confluences that now dominate parasite export, and deploying rapid response teams to contain reintroduction events before they become reestablishment. Brazil’s elimination deadlines remain technically within reach, the study suggests, but only if the country learns to track not just where malaria is, but where it is going next.

Subject of Research: Human mobility and malaria reintroduction in the Brazilian Amazon

Article Title: Mobility hinders malaria elimination goals in the Brazilian Amazon

Article References: Arisco, N. J., Fontoura, P. S., Peterka, C., & Castro, M. C. (2026). Mobility hinders malaria elimination goals in the Brazilian Amazon. PLOS Computational Biology, 22(10), e1014843. https://doi.org/10.1371/journal.pcbi.1014843

Image Credits: AI Generated

DOI: 10.1371/journal.pcbi.1014843

Keywords: malaria, Brazilian Amazon, Plasmodium falciparum, Plasmodium vivax, human mobility, mining, Yanomami Indigenous Land, malaria elimination, reintroduction, disease surveillance, deforestation, PLOS Computational Biology