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Microbiology Spectrum Jun 2024Malaria infection remains a serious threat to human health worldwide. Rapid and accurate detection technology is crucial for preventing malaria transmission and...
UNLABELLED
Malaria infection remains a serious threat to human health worldwide. Rapid and accurate detection technology is crucial for preventing malaria transmission and minimizing damage. We aimed to establish and validate a new rapid molecular detection method for malaria, called EasyNAT Malaria Assay, targeting , , , and . The analytical performance of EasyNAT Malaria Assay was determined using positive materials. We identified 42 clinical samples as malaria positive and 95 negative samples. Each sample was examined by four methods: light microscopy, rapid diagnostic test, EasyNAT Malaria Assay, and digital PCR. Diagnostic accuracy and clinical performance were evaluated. The limit of detection (LOD) of EasyNAT Malaria was consistently 40 parasites/mL. It specifically amplified and performed with reliable repeatability and reproducibility. In 137 clinical samples, EasyNAT Malaria detected four more positive samples than microscopic examination and two more positive samples than rapid diagnostic test (RDT). One clinical sample was positive only under digital PCR. However, no significant differences statistically in sensitivity or specificity were observed. Compared with microscopy, the total, positive, and negative concordance rates of EasyNAT were 97.08%, 100%, and 95.79%, respectively. Enhanced diagnostic accuracy of EasyNAT Malaria in patients who had taken anti-malarial medication before their clinical appointment was observed. The EasyNAT Malaria Assay has good detection efficiency for clinical samples, presents a promising molecular detection tool in clinical practice, and is particularly suitable for rapid screening of high-risk populations in the emergency room.
IMPORTANCE
This study established and validated EasyNAT Malaria Assay as a promising molecular detection tool for malaria screening of high-risk populations in clinical practice. This novel isothermal amplification method may effectively facilitate the rapid diagnosis of malaria and prevent its transmission.
PubMed: 38869308
DOI: 10.1128/spectrum.00583-24 -
Nature Jun 2024Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular...
Malaria-causing protozoa of the genus Plasmodium have exerted one of the strongest selective pressures on the human genome, and resistance alleles provide biomolecular footprints that outline the historical reach of these species. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe. To address these questions, we generated high-coverage ancient mitochondrial and nuclear genome-wide data from P. falciparum, P. vivax and P. malariae from 16 countries spanning around 5,500 years of human history. We identified P. vivax and P. falciparum across geographically disparate regions of Eurasia from as early as the fourth and first millennia BCE, respectively; for P. vivax, this evidence pre-dates textual references by several millennia. Genomic analysis supports distinct disease histories for P. falciparum and P. vivax in the Americas: similarities between now-eliminated European and peri-contact South American strains indicate that European colonizers were the source of American P. vivax, whereas the trans-Atlantic slave trade probably introduced P. falciparum into the Americas. Our data underscore the role of cross-cultural contacts in the dissemination of malaria, laying the biomolecular foundation for future palaeo-epidemiological research into the impact of Plasmodium parasites on human history. Finally, our unexpected discovery of P. falciparum in the high-altitude Himalayas provides a rare case study in which individual mobility can be inferred from infection status, adding to our knowledge of cross-cultural connectivity in the region nearly three millennia ago.
PubMed: 38867050
DOI: 10.1038/s41586-024-07546-2 -
PLoS Neglected Tropical Diseases Jun 2024Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The...
BACKGROUND
Malaria transmission-blocking vaccines (TBVs) aim to inhibit malaria parasite development in mosquitoes and prevent further transmission to the human host. The putative-secreted ookinete protein 25 (PSOP25), highly conserved in Plasmodium spp., is a promising TBV target. Here, we investigated PvPSOP25 from P. vivax as a TBV candidate using transgenic murine parasite P. berghei and clinical P. vivax isolates.
METHODS AND FINDINGS
A transgenic P. berghei line expressing PvPSOP25 (TrPvPSOP25Pb) was generated. Full-length PvPSOP25 was expressed in the yeast Pichia pastoris and used to immunize mice to obtain anti-rPvPSOP25 sera. The transmission-blocking activity of the anti-rPvPSOP25 sera was evaluated through in vitro assays and mosquito-feeding experiments. The antisera generated by immunization with rPvPSOP25 specifically recognized the native PvPSOP25 antigen expressed in TrPvPSOP25Pb ookinetes. In vitro assays showed that the immune sera significantly inhibited exflagellation and ookinete formation of the TrPvPSOP25Pb parasite. Mosquitoes feeding on mice infected with the transgenic parasite and passively transferred with the anti-rPvPSOP25 sera showed a 70.7% reduction in oocyst density compared to the control group. In a direct membrane feeding assay conducted with five clinical P. vivax isolates, the mouse anti-rPvPSOP25 antibodies significantly reduced the oocyst density while showing a negligible influence on mosquito infection prevalence.
CONCLUSIONS
This study supported the feasibility of transgenic murine malaria parasites expressing P. vivax antigens as a useful tool for evaluating P. vivax TBV candidates. Meanwhile, the moderate transmission-reducing activity of the generated anti-rPvPSOP25 sera necessitates further research to optimize its efficacy.
Topics: Animals; Mice; Plasmodium vivax; Malaria Vaccines; Plasmodium berghei; Protozoan Proteins; Humans; Malaria, Vivax; Female; Antigens, Protozoan; Antibodies, Protozoan; Malaria; Mice, Inbred BALB C
PubMed: 38865344
DOI: 10.1371/journal.pntd.0012231 -
Journal of Korean Medical Science Jun 2024Malaria elimination strategies in the Republic of Korea (ROK) have decreased malaria incidence but face challenges due to delayed case detection and response. To improve...
BACKGROUND
Malaria elimination strategies in the Republic of Korea (ROK) have decreased malaria incidence but face challenges due to delayed case detection and response. To improve this, machine learning models for predicting malaria, focusing on high-risk areas, have been developed.
METHODS
The study targeted the northern region of ROK, near the demilitarized zone, using a 1-km grid to identify areas for prediction. Grid cells without residential buildings were excluded, leaving 8,425 cells. The prediction was based on whether at least one malaria case was reported in each grid cell per month, using spatial data of patient locations. Four algorithms were used: gradient boosted (GBM), generalized linear (GLM), extreme gradient boosted (XGB), and ensemble models, incorporating environmental, sociodemographic, and meteorological data as predictors. The models were trained with data from May to October (2019-2021) and tested with data from May to October 2022. Model performance was evaluated using the area under the receiver operating characteristic curve (AUROC).
RESULTS
The AUROC of the prediction models performed excellently (GBM = 0.9243, GLM = 0.9060, XGB = 0.9180, and ensemble model = 0.9301). Previous malaria risk, population size, and meteorological factors influenced the model most in GBM and XGB.
CONCLUSION
Machine-learning models with properly preprocessed malaria case data can provide reliable predictions. Additional predictors, such as mosquito density, should be included in future studies to improve the performance of models.
Topics: Republic of Korea; Humans; Malaria, Vivax; Machine Learning; Plasmodium vivax; ROC Curve; Algorithms; Area Under Curve; Incidence; Risk Factors
PubMed: 38859739
DOI: 10.3346/jkms.2024.39.e176 -
Malaria Journal Jun 2024Plasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been...
BACKGROUND
Plasmodium vivax malaria is a leading cause of morbidity in Ethiopia. The first-line treatment for P. vivax is chloroquine (CQ) and primaquine (PQ), but there have been local reports of CQ resistance. A clinical study was conducted to determine the efficacy of CQ for the treatment of P. vivax malaria in southern Ethiopia.
METHODS
In 2021, patients with P. vivax mono-infection and uncomplicated malaria were enrolled and treated with 25 mg/kg CQ for 3 consecutive days. Patients were followed for 28 days according to WHO guidelines. The data were analysed using per-protocol (PP) and Kaplan‒Meier (K‒M) analyses to estimate the risk of recurrent P. vivax parasitaemia on day 28.
RESULTS
A total of 88 patients were enrolled, 78 (88.6%) of whom completed the 28 days of follow-up. Overall, 76 (97.4%) patients had adequate clinical and parasitological responses, and two patients had late parasitological failures. The initial therapeutic response was rapid, with 100% clearance of asexual parasitaemia within 48 h.
CONCLUSION
Despite previous reports of declining chloroquine efficacy against P. vivax, CQ retains high therapeutic efficacy in southern Ethiopia, supporting the current national treatment guidelines. Ongoing clinical monitoring of CQ efficacy supported by advanced molecular methods is warranted to inform national surveillance and ensure optimal treatment guidelines.
Topics: Malaria, Vivax; Chloroquine; Ethiopia; Humans; Antimalarials; Male; Adult; Female; Adolescent; Young Adult; Child; Middle Aged; Child, Preschool; Plasmodium vivax; Treatment Outcome; Aged; Parasitemia
PubMed: 38858696
DOI: 10.1186/s12936-024-05009-7 -
MSMR May 2024MSMR publishes annual updates on the incidence of malaria among U.S. service members. Malaria infection remains a potential health threat to U.S. service members located...
MSMR publishes annual updates on the incidence of malaria among U.S. service members. Malaria infection remains a potential health threat to U.S. service members located in or near endemic areas due to duty assignment, participation in contingency operations, or personal travel. In 2023, a total of 39 active and reserve component service members were diagnosed with or reported to have malaria, an 8.3% increase from the 36 cases identified in 2022. Over half of the malaria cases in 2023 were caused by Plasmodium falciparum (53.8%; n=21) followed by unspecified types of malaria (35.9%; n=14) and P vivax and other Plasmodia (5.1%; n=2 each ). Malaria cases were diagnosed or reported from 22 different medical facilities: 18 in the U.S., 2 in Germany, 1 in Africa, 1 in South Korea. Of the 33 cases with known locations of diagnoses, 6 (18.2%) were reported from or diagnosed outside the U.S.
Topics: Humans; United States; Military Personnel; Incidence; Malaria; Male; Female; Adult; Population Surveillance; Young Adult; Malaria, Falciparum
PubMed: 38857496
DOI: No ID Found -
Iranian Journal of Microbiology Apr 2024Malaria was the first ever reported case of transfusion transmitted infection (TTI). Transfusion transmissible malaria (TTM) can result in febrile transfusion reaction...
BACKGROUND AND OBJECTIVES
Malaria was the first ever reported case of transfusion transmitted infection (TTI). Transfusion transmissible malaria (TTM) can result in febrile transfusion reaction in the recipient. TTM can be fatal if the blood transfusion recipient is from vulnerable population i.e. pregnant women or young children. Therefore, the present study was done to estimate the seroprevalence of malaria parasitemia among blood donors in Garhwal region.
MATERIALS AND METHODS
Study subjects were healthy blood donors who had passed the screening criteria for blood donation. Donors with a history of malaria were temporarily deferred for 3 months following full recovery. Screening of the donated blood units for malaria parasite was done using immunochromatography based rapid diagnostic test. Thin smear examination was performed for malaria parasite species identification.
RESULTS
A total of 1984 blood donations were screened for TTI. The seroprevalence of HBV, HCV HIV and syphilis was 0.3% (n=6), 0.25% (n=5), 0% (n=0) and 0% (n=0) respectively. The seroprevalence of malaria parasite was 0.05% (n=1). was identified upon thin smear examination. The donor reactive for malaria parasite was a replacement donor and gave no recent history of fever or any past history of malaria.
CONCLUSION
Meticulous donor screening combined with rapid diagnostic tests for malaria parasite is the most practical strategy to prevent TTM in Garhwal region of India.
PubMed: 38854983
DOI: 10.18502/ijm.v16i2.15360 -
PLoS Neglected Tropical Diseases Jun 2024Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such...
Effective radical cure of Plasmodium vivax malaria is essential for malaria elimination in Brazil. P. vivax radical cure requires administration of a schizonticide, such as chloroquine, plus an 8-aminoquinoline. However, 8-aminoquinolines cause hemolysis in individuals with glucose-6-phosphate dehydrogenase (G6PD) deficiency, requiring prior screening to exclude those at risk. Brazil is pioneering the implementation of tafenoquine, a single-dose 8-aminoquinoline indicated for P. vivax patients with >70% of normal G6PD activity. Tafenoquine implementation in Manaus and Porto Velho, two municipalities located in the western Brazilian Amazon, included comprehensive training of healthcare professionals (HCPs) on point-of-care quantitative G6PD testing and a new treatment algorithm for P. vivax radical cure incorporating tafenoquine. Training was initially provided to higher-level facilities (phase one) and later adapted for primary care units (phase two). This study analyzed HCP experiences during training and implementation and identified barriers and facilitators. In-depth interviews and focus discussion groups were conducted 30 days after each training for a purposive random sample of 115 HCPs. Thematic analysis was employed using MAXQDA software, analyzing data through inductive and deductive coding. Analysis showed that following the initial training for higher-level facilities, some HCPs did not feel confident performing quantitative G6PD testing and prescribing the tafenoquine regimen. Modifications to the training in phase two resulted in an improvement in understanding the implementation process of the G6PD test and tafenoquine, as well as in the knowledge acquired by HCPs. Additionally, knowledge gaps were addressed through in situ training, peer communication via a messaging app, and educational materials. Training supported effective deployment of the new tools in Manaus and Porto Velho and increased awareness of the need for pharmacovigilance. A training approach for nationwide implementation of these tools was devised. Implementing quantitative G6PD testing and tafenoquine represents a significant shift in P. vivax malaria case management. Consistent engagement with HCPs is needed to overcome challenges in fully integrating these tools within the Brazilian health system.
Topics: Humans; Brazil; Malaria, Vivax; Antimalarials; Aminoquinolines; Glucosephosphate Dehydrogenase Deficiency; Health Personnel; Female; Glucosephosphate Dehydrogenase; Male; Plasmodium vivax; Adult
PubMed: 38837977
DOI: 10.1371/journal.pntd.0012197 -
Antimicrobial Agents and Chemotherapy Jun 2024The human malaria- monkey model has served the malaria research community since its inception in 1966 at the Gorgas Memorial Laboratory (GML) in Panama. Spanning over... (Review)
Review
The human malaria- monkey model has served the malaria research community since its inception in 1966 at the Gorgas Memorial Laboratory (GML) in Panama. Spanning over five decades, this model has been instrumental in evaluating the efficacy and pharmacokinetics of a wide array of candidate antimalarial drugs, whether used singly or in combination. The animal model could be infected with drug-resistant and susceptible and strains that follow a characteristic and reproducible course of infection, remarkably like human untreated and treated infections. Over the years, the model has enabled the evaluation of several synthetic and semisynthetic endoperoxides, for instance, artelinic acid, artesunate, artemether, arteether, and artemisone. These compounds have been evaluated alone and in combination with long-acting partner drugs, commonly referred to as artemisinin-based combination therapies, which are recommended as first-line treatment against uncomplicated malaria. Further, the model has also supported the evaluation of the primaquine analog tafenoquine against blood stages of , contributing to its progression to clinical trials and eventual approval. Besides, the / model at GML has also played a pivotal role in exploring the biology, immunology, and pathogenesis of malaria and in the characterization of drug-resistant and strains. This minireview offers a historical overview of the most significant contributions made by the Panamanian owl monkey () to malaria chemotherapy research.
PubMed: 38837364
DOI: 10.1128/aac.00338-24 -
Frontiers in Cellular and Infection... 2024Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by . Previous studies have...
Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by . Previous studies have demonstrated that extracellular vesicles (EVs) secreted from infected reticulocytes facilitate binding to human spleen fibroblasts (hSFs) and identified parasite genes whose expression was dependent on an intact spleen. Here, we characterize the spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named (PvSDP1), was located at the surface of infected red blood cells in the transgenic line and this localization was later confirmed in natural infections. Plasma-derived EVs from -infected individuals (PvEVs) significantly increased cytoadherence of 3D7_PvSDP1 transgenic line to hSFs and this binding was inhibited by anti-PvSDP1 antibodies. Single-cell RNAseq of PvEVs-treated hSFs revealed increased expression of adhesion-related genes. These findings demonstrate the importance of parasite spleen-dependent genes and EVs from natural infections in the formation of intrasplenic niches in , a major challenge for malaria elimination.
Topics: Extracellular Vesicles; Plasmodium vivax; Humans; Spleen; Malaria, Vivax; Protozoan Proteins; Erythrocytes; Fibroblasts; Plasmodium falciparum; Cell Adhesion; Host-Parasite Interactions
PubMed: 38828264
DOI: 10.3389/fcimb.2024.1408451