Search Results (163)

Background: In sub-Saharan Africa, Plasmodium falciparum is unequivocally responsible for almost all malaria cases and deaths. However, the long-neglected human P. vivax, P. ovale, and P. malariae parasites also emerge as relevant, though their prevalence and contribution to the burden of the disease are very poorly appreciated. This study aimed to bridge this gap and surveyed the circulation of non-falciparum malaria parasites among febrile patients in four regions in south Senegal. Methods: Blood samples were obtained from 1990 febrile patients during the malaria transmission seasons of 2020, 2021, and 2022 in four southern regions in Senegal (Kedougou, Kolda, Tambacounda, and Ziguinchor). Genomic DNA was isolated and tested for Plasmodium infections by using a combination of Plasmodium genus-specific qPCR and Plasmodium species-specific nested PCR. Frequencies and distribution of Plasmodium species according to region, period, and patient demographics were analyzed using R. Spatial patterns of infection were further explored and visualized with QGIS software version 3.30.2. Results: The Plasmodium positivity rate was 73.43% of which 67.92% were unique Plasmodium species infections and 32.08% were co-infections by two or three Plasmodium species. The results described the ongoing circulation of all non-falciparum species in three of the four study regions, the non-detection of P. vivax and P. malariae parasites among the samples tested in Ziguinchor, the first evidence of non-falciparum infections in Kolda and Tambacounda, as well as the first report of P. ovale in Ziguinchor. Conclusions: Our data call on clinicians to account for these species in clinical prognoses, but also on the National Malaria Control Programme to consider these species in their policy of reducing the incidence of the disease with a view to eliminating malaria in Senegal. Full article

Background/Objectives: In the Brazilian Amazon, which accounts for over 99% of national malaria cases, 34,260 cases were reported as of August 2025, predominantly caused by Plasmodium vivax, responsible for 86.69% of the infections. The increasing resistance of the parasite to conventional therapies highlights the urgent need for novel control strategies, with essential oils and plant-derived substances emerging as promising alternatives. Methods: In this context, we evaluated the anti-Plasmodium potential of Piper alatipetiolatum essential oil and its major constituent 6-ishwarone against P. vivax, including cytotoxicity in Vero and PBMCs, molecular docking on dihydrofolate reductase (DHFR) and lactate dehydrogenase (LDH), and in silico pharmacokinetic profiling. Results: Both the oil and 6-ishwarone inhibited P. vivax dose-dependently (2.1 ± 1 to 100%), with IC₅₀ values of 9.25 µg/mL and 3.93 µg/mL, respectively. Importantly, no cytotoxic effects were observed at 24 h, with cell viability ranging from 94.7% to 98.3%, highlighting the selectivity of these compounds towards the parasite over mammalian cells. Docking studies indicated selective binding of 6-ishwarone to DHFR (−7.7 kcal/mol; Ki = 2.27 µM) with key interactions (Trp816, Lys820, Tyr819, Asn823, Thr865), whereas binding to LDH was weaker (−6.2 kcal/mol; Ki = 28.10 µM), suggesting DHFR as the primary molecular target. In silico ADMET predictions and experimental data indicated favorable drug-like properties: TPSA = 20.23 Ų, moderate lipophilicity (LogP = 3.37), soluble (ESOL Log S = −3.58; Ali Log S = −3.89; Silicos-IT Log S = −2.84), high gastrointestinal absorption, BBB permeability (0.985), not a P-glycoprotein substrate (0.11), and low likelihood of CYP inhibition. Toxicity predictions showed non-mutagenic and non-hepatotoxic effects, low cardiotoxicity (hERG inhibition risk 0.08–0.32), low reproductive toxicity (0.03), moderate neurotoxicity (0.28), low acute toxicity (oral LD₅₀ = 2.061 mol/kg), and low chronic toxicity (LOAEL = 1.995 log mg/kg/day). Conclusions: Together, these findings demonstrate that essential oil and 6-ishwarone of P. alatipetiolatum are selective, bioavailable, and promising natural leads for antimalarial drug development. Full article

Background: Babesiosis and malaria are infectious diseases caused by the intraerythrocytic parasites Babesia and Plasmodium, respectively. While no human red blood cell (RBC) receptors have been shown to be essential for B. microti (Bm) invasion, Duffy (ACKR1) was reported to be essential for P. knowlesi and P. vivax invasion in 1975 and 1976, respectively. This suggests additional medical progress is needed for babesiosis, warranting a detailed analysis. Methods: Given similarities in the target cell of infection, data about babesiosis and malaria cases in the US were obtained from the Centers for Disease Control and Prevention (CDC). Research funding was quantified using National Institutes of Health (NIH) data, and medical progress was evaluated through a literature review. Results: Over the 5-year span of 2018–22, there were 9799 and 7722 confirmed babesiosis and malaria cases, respectively. Confirmed babesiosis cases exceeded malaria cases in 4 of 5 years. In 2022, babesiosis and malaria data were either not reported or unavailable to the CDC by ten and one US state(s), respectively. Regarding babesiosis, it is likely that the vast majority of cases were due to domestically acquired Bm, in the context of no chemoprophylaxis. Concerning malaria, >90% of US cases were imported from foreign locations, ~95% of cases were linked with not taking chemoprophylaxis, and P. falciparum (Pf) was the most common cause. From 2018–22, babesiosis and malaria were the underlying cause of death for 70 and 32 US residents, respectively. NIH funding estimates suggest ~$4 million in support of babesiosis and ~$169 million for malaria in 2024. There are many malaria-inspired medications, two malaria vaccines, and hundreds of characterized Plasmodium proteins, while these measures of medical progress are far behind for babesiosis. Outside of the US, there are >200 million malaria cases per year, while babesiosis is rare. Conclusions: In the US from 2018–22, there were more babesiosis cases and deaths than malaria. Decades of robust CDC and NIH funding for malaria led to its elimination from the US, improved medical knowledge and interventions, and reduced foreign morbidity and mortality. These data suggest that leveraging similar approaches used for malaria, including increased NIH and CDC funding for babesiosis, would likely lead to progress (e.g., improved treatment). Babesiosis qualifies as both a rare and an orphan disease. Full article

This study evaluated the molecular resistance profile to insecticides and the genetic diversity of Anopheles albimanus populations from malaria endemic comarcas in Panama, a country in Mesoamerica aiming to eliminate local malaria transmission. Molecular screening was performed in 891 An. albimanus, distributed in 162 pools, and collected between 2011 and 2023. Pools were molecularly examined to detect natural infection with Plasmodium and sequenced to assess mutations in genes (vgsc, ace-1 and rdl) associated with resistance to commonly used insecticides. A high molecular infection rate by Plasmodium vivax was detected in all comarcas throughout the study period, and P. falciparum infections were detected in the last two years (2022–2023) in the east region. Mutations associated with pyrethroids/DDT resistance (H973Y and L1014F/C) and to organophosphorus/carbamate resistance (G119S) were detected at high frequencies (50.8% and 70%, respectively) in eastern comarcas but were absent from comarcas located west of the Panama Canal. Mutations in the rdl gene, associated with resistance to cyclodienes and neonicotinoids, were also frequently present. Anopheles populations from the western side were highly homogenous, suggesting a clonal expansion, contrasting with eastern samples, which exhibited a high genetic diversity. Our study provides a valuable baseline for planning future molecular vector surveillance studies in the region. It also provides valuable information to the vector control program in Panama to guide insecticide selection for IRS. Full article

Malaria remains a considerable challenge to international health, especially in returning travelers from endemic regions where exposure risk may be downplayed. Prompt and accurate diagnosis is crucial, especially when conventional diagnostic techniques are insufficient. This case report presents a 59-year-old man who developed fever, rash, and myalgia after returning from the Amazon rainforest. Initial laboratory tests demonstrated leukopenia, thrombocytopenia, transaminitis, and hyperbilirubinemia. Despite these abnormal results and a clinically suspicious presentation, malaria smears were negative. Since the symptoms did not resolve, a Karius test—a plasma-based microbial cell-free DNA sequencing assay—successfully detected the presence of Plasmodium vivax, thus establishing the diagnosis. The patient needed several treatment regimens for the recurrent attacks, including chloroquine and primaquine, artemether-lumefantrine, and eventually a combination of quinine and doxycycline together with a prolonged course of primaquine. His symptoms resolved completely after the last treatment regimen, along with the normalization of the blood counts and liver function tests. This case demonstrates the limitations of smear microscopy diagnosis in P. vivax infections, highlights the role of molecular diagnostics like the Karius test, and stresses the importance of preventing relapses with adequate hypnozoite clearance. It further highlights the importance of clinician awareness and diligent follow-up in cases of travel-related Malaria, especially those with unusual presentations or recurrent symptoms. Full article

As Honduras approaches malaria elimination, imported infections pose a growing challenge to disease surveillance and control. In this study, we analyzed 14 molecular markers—six from Plasmodium falciparum and eight from P. vivax—in samples from local and migrant subjects to assess their utility in differentiating local versus imported infections. All P. falciparum isolates carried the wild-type pfcrt haplotype associated with chloroquine susceptibility. However, polymorphisms in pfmdr1, pfama1, pfglurp, and pfs47 revealed distinct genotypes in migrant versus local samples, suggesting external origins. For P. vivax, three novel pvcsp VK210 haplotypes and the first detection of a VK247 variant in Honduras were identified in migrants. Additional novel haplotypes were found in pvmsp1, pvmsp3α, pvmsp3β, pvs47, and pvs48/45. Several of these markers—particularly pfmdr1, pfs47, pvs47, and pvs48/45—proved informative for inferring geographic origin. This study demonstrates the value of molecular surveillance in low-transmission settings, supporting public health efforts by identifying potentially imported cases. Full article

Dengue and malaria are common vector-borne tropical diseases and are associated with high morbidity and mortality. Co-infection of dengue and malaria is underestimated due to parsimonious diagnostic approaches once the diagnosis of either is made, particularly using point-of-care assays, such as rapid diagnostic tests (RDTs). We present a case of dengue and Plasmodium vivax co-infection in a returned traveler from an endemic region, in whom the epidemiology and clinical course are highly suggestive of dengue triggering a P. vivax relapse. The literature on the co-occurrence of dengue and malaria in travelers is reviewed, as is the state of knowledge surrounding dengue as a precipitant to relapsing malaria. Full article

In Mexico, Plasmodium vivax transmission has been confined to the northwestern and southern regions since 2000. Parasites from five malaria foci were analyzed using three genetic markers. The circumsporozoite gene was examined by PCR-RFLP and sequencing, and pvs25 mutations and variants of ribosomal 18S SSU rRNA S-type were also determined. Previous data from the southernmost Pacific in Chiapas were included in the analysis. Both the VK210 and VK247 types of pvcsp were detected, and VK210 had greater haplotype diversity (0.860) than VK247 parasites (0.198). Two pvs25 mutations (Q87K and I130T) yielded three haplotypes, and two ribosomal variants were detected. Gene and multilocus haplotype frequencies varied among malarious foci (p < 0.001). An AMOVA test, F_ST values, and Spearman’s correlation suggested a structured P. vivax population among the malaria foci. Each malaria focus across the northwestern and southern regions retained a portion of the past countrywide P. vivax population, which seems unique in Latin America. In the Lacandon region (LR), a linkage equilibrium between pvs25 haplotypes and the ribosomal variants within the VK247 or VK210 populations was observed. This region harbored the broadest reservoir of P. vivax haplotypes, and the high adaptation of parasites in the northwestern region represents a challenge for malaria elimination. These finding are relevant for monitoring and epidemiological surveillance. Full article

Asymptomatic malaria infection is a major concern in the fight against malaria, as it can act as a significant reservoir for its silent spread or transmission. Therefore, surveillance to detect asymptomatic subjects, particularly in regions with high malaria endemicity, is essential. This study aimed to investigate the status of asymptomatic submicroscopic malaria infections in Gia Lai province, Vietnam, and to analyze molecular profiles of antimalarial drug resistance in the parasites from the asymptomatic carriers. A total of 2171 individuals were included from three districts of Gia Lai province, Vietnam, an area where malaria is endemic. Asymptomatic submicroscopic infection was confirmed by quantitative real-time PCR, and the infected Plasmodium species were confirmed by sequencing. Antimalarial drug-resistant genes, including pfk13, pfcrt, pvmdr-1, and pvcrt-o, were analyzed in the parasites from asymptomatic cases. The rate of asymptomatic submicroscopic malaria infection was 2.67%. P. falciparum and P. vivax mono-infections, as well as mixed infections of P. falciparum and P. vivax, were identified, with P. vivax being more prevalent, a significant observation given the challenge of P. vivax relapses and its contribution to sustained malaria transmission. Adults, including young, middle-aged, and older adults, were the predominant affected groups. Asymptomatic infections were more common in females than in males. Interestingly, high frequencies of mutations in genetic markers associated with antimalarial drug resistance, particularly pfk13 (C580Y, 100%), pfcrt (M74I/N75E/K76T, 100%), and pvmdr-1 (F1076L, 100%), were observed in asymptomatic individuals, which may increase the risk of spreading drug resistance. These findings emphasize the urgent necessity for improved surveillance and targeted intervention to prevent the silent spread of malaria, supporting the National Malarial Control and Elimination Program in formulating malaria elimination strategies for Vietnam. Full article

Introduction: Malaria is a tropical disease caused by the parasite Plasmodium sp., which is considered a significant public health challenge, particularly in Africa. Among the species related to human infection, P. falciparum and P. vivax are known for their high incidence and pathogenicity. Despite several approved drugs in the treatment, the increase in resistance mechanisms is becoming increasingly prevalent, which makes the discovery of effective and safer drugs challenging. Thus, it is necessary to explore new mechanisms of action for the discovery of innovative antimalarial agents. Among the explored targets, proteases, especially subtilisin, have shown great promise in the development of new therapeutic options. Method: A narrative review was conducted using the main databases to provide critical information about the subtilisin to design antimalarial drugs. Results: Critical data were found about the isoforms of subtilisins, highlighting SUB1 and SUB2. SBDD approaches were able to show that compounds designed to target the catalytic Asp³⁷², His⁴²⁸, and Ser⁶⁰⁶, and other such Leu⁴⁶⁹, Gly⁴⁶⁷, and Asn⁵²⁰ against SUB1, presented critical results. In addition, quinoline, benzopyran, and triterpene derivatives and peptide inhibitors show their importance, and these scaffolds can be explored in further work. Conclusions: Considering the relevance of this target, this review provided insights into medicinal chemistry, the discovery of antimalarial drugs that act by inhibiting subtilisin, and promoted a promising initiative to combat malaria. Full article

Malaria is a parasitic disease caused by Plasmodium protozoa, which is a serious public health issue in Madagascar, an island country located off the coast of Africa in the Indian Ocean. Despite significant efforts to prevent the spread of communicable diseases, the country’s epidemiological situation is worrying and has been deteriorating in recent years, mostly due to poverty and limited access to healthcare. The aim of the present study was to assess the prevalence rates of malaria in northern Madagascar, as exemplified by the Mampikony District, between 2023 and 2024, as well as to assess the effectiveness of the methods used for malaria diagnosis. Material and methods. The study was conducted on a sample of 782 local residents who reported to healthcare centres in Mampikony between 2023 and 2024. The methods used to establish the diagnosis of malaria included rapid diagnostic tests (mRDTs) and molecular assays (RT-PCRs). Results. The 2023 study conducted on a sample of 484 patients demonstrated malaria prevalence of 4.5% (by mRDTs) and 8.2% (by RT-PCR), while the 2024 study carried out on a sample of 298 patients demonstrated malaria prevalence of 8.4% (by mRDTs) and 12.4% (by RT-PCR). The analysis of demographic variables showed that malaria was more prevalent in women and in adults; however, the differences between individual study groups were not statistically significant. In this study, positive malaria cases were predominantly caused by P. falciparum, but we also found cases caused by P. vivax as well as mixed infections. Conclusions. The study results support the need to apply more sensitive diagnostic tools for malaria diagnosis, e.g., RT-PCR. Also, our findings indicate the necessity to reassess and update the strategies for the treatment of malaria in the region due to a growing asymptomatic malaria carriage. To control the spread of malaria in Madagascar, it is essential to apply a wide range of interventions. Full article

Identifying the diversity of wildlife hosts for malaria parasites in wildlife is crucial for understanding transmission dynamics in endemic regions where humans, vectors, and wildlife heavily overlap. We examined the presence of Plasmodium parasites in free-ranging ring-tailed coatis (Nasua nasua, n = 44) and nine-banded armadillos (Dasypus novemcinctus, n = 66) from an Indigenous community in the Peruvian Amazon. Nested PCR targeting the mitochondrial cytb gene detected Plasmodium spp. DNA in two coatis (4.7%). Sequencing revealed one lineage identical to Plasmodium vivax/P. simium and another to P. malariae/P. brasilianum. A subset of samples was reanalyzed using cox3-based PCR and sequencing in an independent laboratory, confirming P. malariae/P. brasilianum in one coati. No infections were observed in armadillos. These results indicate that coatis in the wild may host diverse Plasmodiidae parasites and that coatis may even carry Plasmodium spp., likely as incidental hosts. Expanding surveillance to additional non-primate mammals will help clarify their role in sylvatic malaria ecology and evaluate potential zoonotic risks. Full article

Given the overlap of epidemiological and clinical presentations of both rickettsioses and malaria infections, diagnostic testing where malaria is confirmed or excluded, without subsequent rickettsial testing, specifically in the case of Plasmodium vivax or P. ovale infection, may mask the possibility of relapse. A lack of clinical suspicion of co-infections, absence of knowledge on the geographic distribution of diseases, and lack of availability of point-of-care diagnostic testing for other tropical diseases can often lead to missed diagnosis or misdiagnosis of common tropical infections, including rickettsioses. We herein describe a case of confirmed intercurrent rickettsial and P. vivax infection, with the former potentially triggering a relapse of the latter in a febrile traveler returning to Canada from South America, and review the literature on tropical coinfections in returning travelers. Full article

In Brazil, Plasmodium infections in non-human primates (NHPs) have been associated with P. simium and P. brasilianum, which are morphologically and genetically similar to the human-infecting species P. vivax and P. malariae, respectively. Surveillance and monitoring of wild NHPs are crucial for understanding the distribution of these parasites and assessing the risk of zoonotic transmission. This study aimed to detect the presence of Plasmodium spp. genetic material in Platyrrhini primates from 47 municipalities in the states of Bahia and Minas Gerais. The animals were captured using Tomahawk-type live traps baited with fruit or immobilized with tranquilizer darts. Free-ranging individuals were chemically restrained via inhalation anesthesia using VetBag^® or intramuscular anesthesia injection. Blood samples were collected from the femoral vein. A total of 298 blood and tissue samples were collected from 10 primate species across five genera: Alouatta caraya (25), Alouatta guariba clamitans (1), Callicebus melanochir (1), Callithrix geoffroyi (28), Callithrix jacchus (4), Callithrix kuhlii (31), Callithrix penicillata (175), Callithrix spp. hybrids (15), Leontopithecus chrysomelas (16), Sapajus robustus (1), and Sapajus xanthosthernos (1). Molecular diagnosis was performed using a nested PCR targeting the 18S small subunit ribosomal RNA (18S SSU rRNA) gene, followed by sequencing. Of the 298 samples analyzed, only one (0.3%) from Bahia tested positive for Plasmodium brasilianum/P. malariae. This represents the first detection of this parasite in a free-living C. geoffroyi in Brazil. These findings highlight the importance of continued surveillance of Plasmodium infections in NHPs to identify regions at risk for zoonotic transmission. Full article

Plasmodium vivax malaria continues to pose a significant and enduring public health challenge across the Americas. Transmission-blocking vaccines (TBVs), which target gametocyte surface antigens such as Pvs47 and Pvs48/45, are being investigated as promising tools to interrupt transmission and advance toward disease elimination. To investigate the genetic diversity and phylogeographic structure of the pvs47 and pvs48/45 genes in P. vivax, we conducted molecular analyses on samples collected from seven malaria-endemic regions of Honduras using PCR-based sequencing, population genetics, and phylogenetic approaches. This study presents the first complete characterization of the pvs47 gene and expands the available data on pvs48/45 in P. vivax from Honduras. We observed a low level of genetic diversity with no evidence of geographic structuring within the country. At a global scale, Honduran sequences shared variants with other Latin American strains and exhibited region-specific amino acid signatures. These findings suggest that local selective pressures, possibly driven by mosquito vector compatibility, are shaping the evolution of these TBV candidate genes. Our results underscore the importance of regional surveillance to inform the development and deployment of effective transmission-blocking strategies. Full article