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1.
PLoS One ; 19(7): e0304337, 2024.
Article in English | MEDLINE | ID: mdl-38968216

ABSTRACT

BACKGROUND: Plasmodium vivax has become the predominant species in the border regions of Thailand. The emergence and spread of antimalarial drug resistance in P. vivax is one of the significant challenges for malaria control. Continuous surveillance of drug resistance is therefore necessary for monitoring the development of drug resistance in the region. This study aims to investigate the prevalence of the mutation in the P. vivax multidrug resistant 1 (Pvmdr1), dihydrofolate reductase (Pvdhfr), and dihydropteroate synthetase (Pvdhps) genes conferred resistance to chloroquine (CQ), pyrimethamine (P) and sulfadoxine (S), respectively. METHOD: 100 P. vivax isolates were obtained between January to May 2023 from a Kanchanaburi province, western Thailand. Nucleotide sequences of Pvmdr1, Pvdhfr, and Pvdhps genes were amplified and sequenced. The frequency of single nucleotide polymorphisms (SNPs)-haplotypes of drug-resistant alleles was assessed. The linkage disequilibrium (LD) tests were also analyzed. RESULTS: In Pvmdr1, T958M, Y976F, and F1076L, mutations were detected in 100%, 21%, and 23% of the isolates, respectively. In Pvdhfr, the quadruple mutant allele (I57R58M61T117) prevailed in 84% of the samples, followed by (L57R58M61T117) in 11%. For Pvdhps, the double mutant allele (G383G553) was detected (48%), followed by the triple mutant allele (G383M512G553) (47%) of the isolates. The most prevalent combination of Pvdhfr (I57R58M61T117) and Pvdhps (G383G553) alleles was sextuple mutated haplotypes (48%). For LD analysis, the association in the SNPs pairs was found between the intragenic and intergenic regions of the Pvdhfr and Pvdhps genes. CONCLUSION: The study has recently updated the high prevalence of three gene mutations associated with CQ and SP resistance. Genetic monitoring is therefore important to intensify in the regions to further assess the spread of drug resistant. Our data also provide evidence on the distribution of drug resistance for the early warning system, thereby threatening P. vivax malaria treatment policy decisions at the national level.


Subject(s)
Antimalarials , Drug Resistance , Malaria, Vivax , Plasmodium vivax , Polymorphism, Single Nucleotide , Plasmodium vivax/genetics , Plasmodium vivax/drug effects , Plasmodium vivax/isolation & purification , Thailand/epidemiology , Drug Resistance/genetics , Humans , Antimalarials/pharmacology , Malaria, Vivax/parasitology , Malaria, Vivax/epidemiology , Malaria, Vivax/drug therapy , Tetrahydrofolate Dehydrogenase/genetics , Linkage Disequilibrium , Mutation , Protozoan Proteins/genetics , Chloroquine/pharmacology , Dihydropteroate Synthase/genetics , Sulfadoxine/pharmacology , Pyrimethamine/pharmacology , Multidrug Resistance-Associated Proteins/genetics , Haplotypes , Male , Female , Adult
2.
PeerJ ; 12: e17632, 2024.
Article in English | MEDLINE | ID: mdl-38948214

ABSTRACT

Background: The integration of diagnostic methods holds promise for advancing the surveillance of malaria transmission in both endemic and non-endemic regions. Serological assays emerge as valuable tools to identify and delimit malaria transmission, serving as a complementary method to rapid diagnostic tests (RDT) and thick smear microscopy. Here, we evaluate the potential of antibodies directed against peptides encompassing the entire amino acid sequence of the PvMSP-1 Sal-I strain as viable serological biomarkers for P. vivax exposure. Methods: We screened peptides encompassing the complete amino acid sequence of the Plasmodium vivax Merozoite Surface Protein 1 (PvMSP-1) Sal-I strain as potential biomarkers for P. vivax exposure. Here, immunodominant peptides specifically recognized by antibodies from individuals infected with P. vivax were identified using the SPOT-synthesis technique followed by immunoblotting. Two 15-mer peptides were selected based on their higher and specific reactivity in immunoblotting assays. Subsequently, peptides p70 and p314 were synthesized in soluble form using SPPS (Solid Phase Peptide Synthesis) and tested by ELISA (IgG, and subclasses). Results: This study unveils the presence of IgG antibodies against the peptide p314 in most P. vivax-infected individuals from the Brazilian Amazon region. In silico B-cell epitope prediction further supports the utilization of p314 as a potential biomarker for evaluating malaria transmission, strengthened by its amino acid sequence being part of a conserved block of PvMSP-1. Indeed, compared to patients infected with P. falciparum and uninfected individuals never exposed to malaria, P. vivax-infected patients have a notably higher recognition of p314 by IgG1 and IgG3.


Subject(s)
Antibodies, Protozoan , Biomarkers , Malaria, Vivax , Merozoite Surface Protein 1 , Plasmodium vivax , Humans , Malaria, Vivax/immunology , Malaria, Vivax/blood , Malaria, Vivax/parasitology , Malaria, Vivax/transmission , Malaria, Vivax/diagnosis , Merozoite Surface Protein 1/immunology , Plasmodium vivax/immunology , Biomarkers/blood , Antibodies, Protozoan/immunology , Antibodies, Protozoan/blood , Immunoglobulin G/immunology , Immunoglobulin G/blood , Adult , Female , Male , Middle Aged , Peptides/immunology , Enzyme-Linked Immunosorbent Assay/methods , Young Adult , Adolescent , Amino Acid Sequence
3.
Malar J ; 23(1): 194, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38902674

ABSTRACT

BACKGROUND: Malaria remains a severe parasitic disease, posing a significant threat to public health and hindering economic development in sub-Saharan Africa. Ethiopia, a malaria endemic country, is facing a resurgence of the disease with a steadily rising incidence. Conventional diagnostic methods, such as microscopy, have become less effective due to low parasite density, particularly among Duffy-negative human populations in Africa. To develop comprehensive control strategies, it is crucial to generate data on the distribution and clinical occurrence of Plasmodium vivax and Plasmodium falciparum infections in regions where the disease is prevalent. This study assessed Plasmodium infections and Duffy antigen genotypes in febrile patients in Ethiopia. METHODS: Three hundred febrile patients visiting four health facilities in Jimma town of southwestern Ethiopia were randomly selected during the malaria transmission season (Apr-Oct). Sociodemographic information was collected, and microscopic examination was performed for all study participants. Plasmodium species and parasitaemia as well as the Duffy genotype were assessed by quantitative polymerase chain reaction (qPCR) for all samples. Data were analysed using Fisher's exact test and kappa statistics. RESULTS: The Plasmodium infection rate by qPCR was 16% (48/300) among febrile patients, of which 19 (39.6%) were P. vivax, 25 (52.1%) were P. falciparum, and 4 (8.3%) were mixed (P. vivax and P. falciparum) infections. Among the 48 qPCR-positive samples, 39 (13%) were negative by microscopy. The results of bivariate logistic regression analysis showed that agriculture-related occupation, relapse and recurrence were significantly associated with Plasmodium infection (P < 0.001). Of the 300 febrile patients, 85 (28.3%) were Duffy negative, of whom two had P. vivax, six had P. falciparum, and one had mixed infections. Except for one patient with P. falciparum infection, Plasmodium infections in Duffy-negative individuals were all submicroscopic with low parasitaemia. CONCLUSIONS: The present study revealed a high prevalence of submicroscopic malaria infections. Plasmodium vivax infections in Duffy-negative individuals were not detected due to low parasitaemia. In this study, an improved molecular diagnostic tool was used to detect and characterize Plasmodium infections, with the goal of quantifying P. vivax infection in Duffy-negative individuals. Advanced molecular diagnostic techniques, such as multiplex real-time PCR, loop-mediated isothermal amplification (LAMP), and CRISPR-based diagnostic methods. These techniques offer increased sensitivity, specificity, and the ability to detect low-parasite-density infections compared to the employed methodologies.


Subject(s)
Duffy Blood-Group System , Genotype , Malaria, Falciparum , Malaria, Vivax , Plasmodium falciparum , Plasmodium vivax , Duffy Blood-Group System/genetics , Humans , Male , Female , Adult , Adolescent , Young Adult , Malaria, Vivax/diagnosis , Malaria, Vivax/parasitology , Ethiopia/epidemiology , Plasmodium vivax/genetics , Plasmodium vivax/isolation & purification , Middle Aged , Malaria, Falciparum/diagnosis , Malaria, Falciparum/parasitology , Malaria, Falciparum/epidemiology , Child , Plasmodium falciparum/genetics , Plasmodium falciparum/isolation & purification , Child, Preschool , Molecular Diagnostic Techniques/methods , Aged , Infant , Cross-Sectional Studies , Prevalence , Fever/parasitology
4.
Nature ; 631(8019): 125-133, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38867050

ABSTRACT

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 species1. Nevertheless, debate persists over when and how malaria parasites emerged as human pathogens and spread around the globe1,2. 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 millennia3. 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.


Subject(s)
DNA, Ancient , Genome, Mitochondrial , Genome, Protozoan , Malaria , Plasmodium , Female , Humans , Male , Altitude , Americas/epidemiology , Asia/epidemiology , Biological Evolution , Disease Resistance/genetics , DNA, Ancient/analysis , Europe/epidemiology , Genome, Mitochondrial/genetics , Genome, Protozoan/genetics , History, Ancient , Malaria/parasitology , Malaria/history , Malaria/transmission , Malaria/epidemiology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/history , Malaria, Falciparum/parasitology , Malaria, Falciparum/transmission , Malaria, Vivax/epidemiology , Malaria, Vivax/history , Malaria, Vivax/parasitology , Malaria, Vivax/transmission , Plasmodium/genetics , Plasmodium/classification , Plasmodium falciparum/genetics , Plasmodium falciparum/isolation & purification , Plasmodium malariae/genetics , Plasmodium malariae/isolation & purification , Plasmodium vivax/genetics , Plasmodium vivax/isolation & purification
5.
Sci Rep ; 14(1): 13669, 2024 06 13.
Article in English | MEDLINE | ID: mdl-38871839

ABSTRACT

Among the factors affecting the effectiveness of malaria control is poor knowledge of the entomologic drivers of the disease. We investigated anopheline populations as part of a baseline study to implement house screening of windows and doors as a supplementary malaria control tool towards elimination in Jabi Tehnan district, Amhara Regional State of Ethiopia. The samples were surveyed monthly using CDC light traps between June 2020 and May 2021. Mosquito trap density (< 3 mosquitoes/trap) was low, however, with a high overall Plasmodium sporozoite rate (9%; indoor = 4.3%, outdoor = 13.1%) comprising P. falciparum (88.9%) and P. vivax (11.1%). Anopheles gambiae s.l., mostly An. arabiensis, comprised > 80% of total anopheline captures and contributed ~ 42% of Plasmodium-infected mosquitoes. On the other hand, morphologically scored Anopheles funestus s.l., constituting about 6% of anopheline collections, accounted for 50% of sporozoite-infected mosquitoes. Most of the infected An. funestus s.l. specimens (86.7%) were grouped with previously unknown or undescribed Anopheles species previously implicated as a cryptic malaria vector in the western Kenyan highlands, confirming its wider geographic distribution in eastern Africa. Other species with Plasmodium infection included An. longipalpis C, An. theileri, An. demillioni, and An. nili. Cumulatively, 77.8% of the infected mosquitoes occurred outdoors. These results suggest efficient malaria parasite transmission despite the low vector densities, which has implications for effective endpoint indicators to monitor malaria control progress. Additionally, the largely outdoor infection and discovery of previously unknown and cryptic vectors suggest an increased risk of residual malaria transmission and, thus, a constraint on effective malaria prevention and control.


Subject(s)
Anopheles , Mosquito Vectors , Ethiopia/epidemiology , Animals , Anopheles/parasitology , Mosquito Vectors/parasitology , Humans , Malaria/transmission , Malaria/epidemiology , Plasmodium falciparum/isolation & purification , Plasmodium falciparum/pathogenicity , Plasmodium vivax/physiology , Sporozoites , Mosquito Control/methods , Malaria, Vivax/transmission , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Malaria, Falciparum/transmission , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Female
6.
Malar J ; 23(1): 189, 2024 Jun 17.
Article in English | MEDLINE | ID: mdl-38880891

ABSTRACT

BACKGROUND: Malaria, a prominent vector borne disease causing over a million annual cases worldwide, predominantly affects vulnerable populations in the least developed regions. Despite their preventable and treatable nature, malaria remains a global public health concern. In the last decade, India has faced a significant decline in malaria morbidity and mortality. As India pledged to eliminate malaria by 2030, this study examined a decade of surveillance data to uncover space-time clustering and seasonal trends of Plasmodium vivax and Plasmodium falciparum malaria cases in West Bengal. METHODS: Seasonal and trend decomposition using Loess (STL) was applied to detect seasonal trend and anomaly of the time series. Univariate and multivariate space-time cluster analysis of both malaria cases were performed at block level using Kulldorff's space-time scan statistics from April 2011 to March 2021 to detect statistically significant space-time clusters. RESULTS: From the time series decomposition, a clear seasonal pattern is visible for both malaria cases. Statistical analysis indicated considerable high-risk P. vivax clusters, particularly in the northern, central, and lower Gangetic areas. Whereas, P. falciparum was concentrated in the western region with a significant recent transmission towards the lower Gangetic plain. From the multivariate space-time scan statistics, the co-occurrence of both cases were detected with four significant clusters, which signifies the regions experiencing a greater burden of malaria cases. CONCLUSIONS: Seasonal trends from the time series decomposition analysis show a gradual decline for both P. vivax and P. falciparum cases in West Bengal. The space-time scan statistics identified high-risk blocks for P. vivax and P. falciparum malaria and its co-occurrence. Both malaria types exhibit significant spatiotemporal variations over the study area. Identifying emerging high-risk areas of P. falciparum malaria over the Gangetic belt indicates the need for more research for its spatial shifting. Addressing the drivers of malaria transmission in these diverse clusters demands regional cooperation and strategic strategies, crucial steps towards overcoming the final obstacles in malaria eradication.


Subject(s)
Malaria, Falciparum , Malaria, Vivax , Plasmodium vivax , Seasons , India/epidemiology , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Humans , Plasmodium vivax/physiology , Space-Time Clustering , Plasmodium falciparum/physiology
7.
Front Cell Infect Microbiol ; 14: 1408451, 2024.
Article in English | MEDLINE | ID: mdl-38828264

ABSTRACT

Recent studies indicate that human spleen contains over 95% of the total parasite biomass during chronic asymptomatic infections caused by Plasmodium vivax. 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 P. vivax spleen-dependent hypothetical gene (PVX_114580). Using CRISPR/Cas9, PVX_114580 was integrated into P. falciparum 3D7 genome and expressed during asexual stages. Immunofluorescence analysis demonstrated that the protein, which we named P. vivax Spleen-Dependent Protein 1 (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 P. vivax-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 P. vivax, a major challenge for malaria elimination.


Subject(s)
Extracellular Vesicles , Malaria, Vivax , Plasmodium vivax , Protozoan Proteins , Spleen , Extracellular Vesicles/metabolism , Plasmodium vivax/genetics , Plasmodium vivax/metabolism , Humans , Spleen/metabolism , Spleen/parasitology , Malaria, Vivax/parasitology , Protozoan Proteins/metabolism , Protozoan Proteins/genetics , Erythrocytes/parasitology , Erythrocytes/metabolism , Fibroblasts/parasitology , Fibroblasts/metabolism , Plasmodium falciparum/genetics , Plasmodium falciparum/metabolism , Plasmodium falciparum/physiology , Cell Adhesion , Host-Parasite Interactions
8.
PLoS Negl Trop Dis ; 18(6): e0012231, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38865344

ABSTRACT

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.


Subject(s)
Malaria Vaccines , Malaria, Vivax , Plasmodium berghei , Plasmodium vivax , Protozoan Proteins , Animals , Mice , Plasmodium vivax/genetics , Plasmodium vivax/immunology , Malaria Vaccines/immunology , Malaria Vaccines/administration & dosage , Plasmodium berghei/genetics , Plasmodium berghei/immunology , Protozoan Proteins/genetics , Protozoan Proteins/immunology , Humans , Malaria, Vivax/transmission , Malaria, Vivax/parasitology , Malaria, Vivax/prevention & control , Malaria, Vivax/immunology , Female , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology , Antibodies, Protozoan/blood , Antibodies, Protozoan/immunology , Malaria/transmission , Malaria/prevention & control , Malaria/parasitology , Malaria/immunology , Mice, Inbred BALB C
9.
J Math Biol ; 89(1): 7, 2024 May 21.
Article in English | MEDLINE | ID: mdl-38772937

ABSTRACT

Malaria is a vector-borne disease that exacts a grave toll in the Global South. The epidemiology of Plasmodium vivax, the most geographically expansive agent of human malaria, is characterised by the accrual of a reservoir of dormant parasites known as hypnozoites. Relapses, arising from hypnozoite activation events, comprise the majority of the blood-stage infection burden, with implications for the acquisition of immunity and the distribution of superinfection. Here, we construct a novel model for the transmission of P. vivax that concurrently accounts for the accrual of the hypnozoite reservoir, (blood-stage) superinfection and the acquisition of immunity. We begin by using an infinite-server queueing network model to characterise the within-host dynamics as a function of mosquito-to-human transmission intensity, extending our previous model to capture a discretised immunity level. To model transmission-blocking and antidisease immunity, we allow for geometric decay in the respective probabilities of successful human-to-mosquito transmission and symptomatic blood-stage infection as a function of this immunity level. Under a hybrid approximation-whereby probabilistic within-host distributions are cast as expected population-level proportions-we couple host and vector dynamics to recover a deterministic compartmental model in line with Ross-Macdonald theory. We then perform a steady-state analysis for this compartmental model, informed by the (analytic) distributions derived at the within-host level. To characterise transient dynamics, we derive a reduced system of integrodifferential equations, likewise informed by our within-host queueing network, allowing us to recover population-level distributions for various quantities of epidemiological interest. In capturing the interplay between hypnozoite accrual, superinfection and acquired immunity-and providing, to the best of our knowledge, the most complete population-level distributions for a range of epidemiological values-our model provides insights into important, but poorly understood, epidemiological features of P. vivax.


Subject(s)
Malaria, Vivax , Mathematical Concepts , Mosquito Vectors , Plasmodium vivax , Superinfection , Humans , Plasmodium vivax/immunology , Plasmodium vivax/physiology , Superinfection/immunology , Superinfection/transmission , Superinfection/parasitology , Malaria, Vivax/transmission , Malaria, Vivax/immunology , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Animals , Mosquito Vectors/parasitology , Mosquito Vectors/immunology , Disease Reservoirs/parasitology , Models, Biological , Computer Simulation , Anopheles/parasitology , Anopheles/immunology
10.
Emerg Infect Dis ; 30(7): 1477-1479, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38710182

ABSTRACT

Beginning in 2023, we observed increased Plasmodium vivax malaria cases at an institution in Los Angeles, California, USA. Most cases were among migrants from China who traveled to the United States through South and Central America. US clinicians should be aware of possible P. vivax malaria among immigrants from China.


Subject(s)
Emigrants and Immigrants , Malaria, Vivax , Plasmodium vivax , Travel , Humans , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , China/epidemiology , United States/epidemiology , Male , Adult , Female , Middle Aged , Young Adult
11.
Infect Genet Evol ; 122: 105605, 2024 Aug.
Article in English | MEDLINE | ID: mdl-38759940

ABSTRACT

Plasmodium vivax Merozoite Surface Protein 8 (PvMSP8) is a promising candidate target for the development of multi-component vaccines. Therefore, determining the genetic variation pattern of Pvmsp8 is essential in providing a reference for the rational design of the P. vivax malaria vaccines. This study delves into the genetic characteristics of the Pvmsp8 gene, specifically focusing on samples from the China-Myanmar border (CMB) region, and contrasts these findings with broader global patterns. The study uncovers that Pvmsp8 exhibits a notable level of conservation across different populations, with limited polymorphisms and relatively low nucleotide diversity (0.00023-0.00120). This conservation contrasts starkly with the high polymorphisms found in other P. vivax antigens such as Pvmsp1. A total of 25 haplotypes and 14 amino acid mutation sites were identified in the global populations, and all mutation sites were confined to non-functional regions. The study also notes that most CMB Pvmsp8 haplotypes are shared among Burmese, Cambodian, Thai, and Vietnamese populations, indicating less geographical variance, but differ notably from those found in Pacific island regions or the Panama. The findings underscore the importance of considering regional genetic diversity in P. vivax when developing targeted malaria vaccines. Non departure from neutral evolution were found by Tajima's D test, however, statistically significant differences were observed between the kn/ks rates. The study's findings are crucial in understanding the evolution and population structure of the Pvmsp8 gene, particularly during regional malaria elimination efforts. The highly conserved nature of Pvmsp8, combined with the lack of mutations in its functional domain, presents it as a promising candidate for developing a broad and effective P. vivax vaccine. This research thus lays a foundation for the rational development of multivalent malaria vaccines targeting this genetically stable antigen.


Subject(s)
Genetic Variation , Haplotypes , Malaria, Vivax , Plasmodium vivax , Protozoan Proteins , Selection, Genetic , Plasmodium vivax/genetics , Protozoan Proteins/genetics , Humans , Malaria, Vivax/parasitology , Malaria, Vivax/epidemiology , Malaria, Vivax/prevention & control , Mutation , Phylogeny , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology
12.
Trends Parasitol ; 40(7): 573-590, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38749866

ABSTRACT

Plasmodium vivax contributes significantly to global malaria morbidity. Key advances include the discovery of pathways facilitating invasion by P. vivax merozoites of nascent reticulocytes, crucial for vaccine development. Humanized mouse models and hepatocyte culture systems have enhanced understanding of hypnozoite biology. The spleen has emerged as a major reservoir for asexual vivax parasites, replicating in an endosplenic life cycle, and contributing to recurrent and chronic infections, systemic inflammation, and anemia. Splenic accumulation of uninfected red cells is the predominant cause of anemia. Recurring and chronic infections cause progressive anemia, malnutrition, and death in young children in high-transmission regions. Endothelial activation likely contributes to vivax-associated organ dysfunction. The many recent advances in vivax pathobiology should help guide new approaches to prevention and management.


Subject(s)
Malaria, Vivax , Plasmodium vivax , Humans , Malaria, Vivax/parasitology , Malaria, Vivax/immunology , Malaria, Vivax/physiopathology , Animals , Plasmodium vivax/physiology , Plasmodium vivax/pathogenicity , Spleen/parasitology , Spleen/physiopathology , Spleen/immunology
13.
Trends Parasitol ; 40(7): 562-572, 2024 Jul.
Article in English | MEDLINE | ID: mdl-38806300

ABSTRACT

The geographic origin of Plasmodium vivax, a leading cause of human malaria, has been the subject of much speculation. Here we review the evolutionary history of P. vivax and P. vivax-like parasites in humans and non-human primates on three continents, providing overwhelming evidence for an African origin. This conclusion is consistent with recent reports showing that Duffy-negative humans in Africa are, in fact, susceptible to P. vivax, with parasites invading Duffy-antigen-expressing erythroid precursors. Thus, the African origin of P. vivax not only explains the distribution of the Duffy-negative genotype but also provides new insight into the history and status of P. vivax malaria in Africa and efforts geared toward its eradication.


Subject(s)
Malaria, Vivax , Plasmodium vivax , Plasmodium vivax/physiology , Plasmodium vivax/genetics , Humans , Animals , Malaria, Vivax/parasitology , Africa , Duffy Blood-Group System/genetics , Primates/parasitology
14.
Parasit Vectors ; 17(1): 239, 2024 May 27.
Article in English | MEDLINE | ID: mdl-38802961

ABSTRACT

BACKGROUND: The spleen plays a critical role in the immune response against malaria parasite infection, where splenic fibroblasts (SFs) are abundantly present and contribute to immune function by secreting type I collagen (collagen I). The protein family is characterized by Plasmodium vivax tryptophan-rich antigens (PvTRAgs), comprising 40 members. PvTRAg23 has been reported to bind to human SFs (HSFs) and affect collagen I levels. Given the role of type I collagen in splenic immune function, it is important to investigate the functions of the other members within the PvTRAg protein family. METHODS: Protein structural prediction was conducted utilizing bioinformatics analysis tools and software. A total of 23 PvTRAgs were successfully expressed and purified using an Escherichia coli prokaryotic expression system, and the purified proteins were used for co-culture with HSFs. The collagen I levels and collagen-related signaling pathway protein levels were detected by immunoblotting, and the relative expression levels of inflammatory factors were determined by quantitative real-time PCR. RESULTS: In silico analysis showed that P. vivax has 40 genes encoding the TRAg family. The C-terminal region of all PvTRAgs is characterized by the presence of a domain rich in tryptophan residues. A total of 23 recombinant PvTRAgs were successfully expressed and purified. Only five PvTRAgs (PvTRAg5, PvTRAg16, PvTRAg23, PvTRAg30, and PvTRAg32) mediated the activation of the NF-κBp65 signaling pathway, which resulted in the production of inflammatory molecules and ultimately a significant reduction in collagen I levels in HSFs. CONCLUSIONS: Our research contributes to the expansion of knowledge regarding the functional role of PvTRAgs, while it also enhances our understanding of the immune evasion mechanisms utilized by parasites.


Subject(s)
Antigens, Protozoan , Collagen Type I , Fibroblasts , Plasmodium vivax , Signal Transduction , Spleen , Plasmodium vivax/genetics , Plasmodium vivax/immunology , Fibroblasts/parasitology , Antigens, Protozoan/genetics , Antigens, Protozoan/immunology , Antigens, Protozoan/metabolism , Animals , Collagen Type I/metabolism , Collagen Type I/genetics , Spleen/immunology , Spleen/parasitology , Transcription Factor RelA/metabolism , Transcription Factor RelA/genetics , Mice , Humans , Malaria, Vivax/parasitology , Malaria, Vivax/immunology , Protozoan Proteins/genetics , Protozoan Proteins/metabolism , Protozoan Proteins/immunology , Tryptophan/metabolism , Escherichia coli/genetics , Escherichia coli/metabolism , Computational Biology
16.
Malar J ; 23(1): 152, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38755638

ABSTRACT

BACKGROUND: Malaria is a major public health concern in Ethiopia, where more than half of the population lives in malaria risk areas. While several studies have been conducted in different eco-epidemiological settings in Ethiopia, there is a notable scarcity of data on the prevalence of malaria in the Gindabarat district. Therefore, this study aimed to analyse 10-year trend of malaria prevalence in Gindabarat district, West Shawa Zone of Oromia, Western Ethiopia. METHODS: A retrospective laboratory record review was conducted at Gindabarat General Hospital and Gindabarat District Health Office from September 2011 to August 2020. The retrieved data included the date of examination, age, sex and laboratory results of the blood smears, including the Plasmodium species identified. Data were summarized and presented in the form of tables, figures, and frequencies to present the results. The data were analysed using SPSS (version 25.0) and Microsoft Excel. RESULTS: Over the course of 10 years, a total of 11,478 blood smears were examined in the public health facilities in the district. Of the total blood smears examined, 1372 (11.95%) were microscopically confirmed malaria. Plasmodium falciparum, Plasmodium vivax and mixed infections (P. falciparum and P. vivax) accounted for 70.77%, 20.55% and 8.67% of the cases, respectively. Malaria prevalence was significantly higher among individuals aged ≥ 15 years (12.60%, x2 = 13.6, df = 2, p = 0.001) and males (14.21%, x2 = 59.7, df = 1, p = 0.001). The highest number of malaria cases was recorded from September to November. CONCLUSION: Malaria remains a public health problem in the district. P. falciparum was the most predominant parasite species in the area. Malaria prevalence was significantly higher among individuals aged ≥ 15 years and males. There was a remarkable fluctuation in the number of malaria cases in different months and years. In the study area malaria cases peaked in 2015 and 2017 then decreasing from 2017 to 2019, with sharp increase in 2020. Moreover, this study showed malaria cases were reported in all seasons and months, but the highest was observed from September to November. Strengthening malaria control activities is essential to further reduce the burden of malaria and pave the way for the anticipated elimination.


Subject(s)
Malaria, Falciparum , Malaria, Vivax , Plasmodium falciparum , Plasmodium vivax , Ethiopia/epidemiology , Prevalence , Male , Humans , Female , Retrospective Studies , Adolescent , Adult , Young Adult , Child , Child, Preschool , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Middle Aged , Infant , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Plasmodium falciparum/isolation & purification , Aged , Infant, Newborn , Aged, 80 and over
17.
Malar J ; 23(1): 149, 2024 May 16.
Article in English | MEDLINE | ID: mdl-38750583

ABSTRACT

BACKGROUND: Malaria elimination in Senegal requires accurate diagnosis of all Plasmodium species. Plasmodium falciparum is the most prevalent species in Senegal, although Plasmodium malariae, Plasmodium ovale, and recently Plasmodium vivax have also been reported. Nonetheless, most malaria control tools, such as Histidine Rich Protein 2 rapid diagnosis test (PfHRP2-RDT,) can only diagnose P. falciparum. Thus, PfHRP2-RDT misses non-falciparum species and P. falciparum infections that fall below the limit of detection. These limitations can be addressed using highly sensitive Next Generation Sequencing (NGS). This study assesses the burden of the four different Plasmodium species in western and eastern regions of Senegal using targeted PCR amplicon sequencing. METHODS: Three thousand samples from symptomatic and asymptomatic individuals in 2021 from three sites in Senegal (Sessene, Diourbel region; Parcelles Assainies, Kaolack region; Gabou, Tambacounda region) were collected. All samples were tested using PfHRP2-RDT and photoinduced electron transfer polymerase chain reaction (PET-PCR), which detects all Plasmodium species. Targeted sequencing of the nuclear 18S rRNA and the mitochondrial cytochrome B genes was performed on PET-PCR positive samples. RESULTS: Malaria prevalence by PfHRP2-RDT showed 9.4% (94/1000) and 0.2% (2/1000) in Diourbel (DBL) and Kaolack (KL), respectively. In Tambacounda (TAM) patients who had malaria symptoms and had a negative PfHRP2-RDT were enrolled. The PET-PCR had a positivity rate of 23.5% (295/1255) overall. The PET-PCR positivity rate was 37.6%, 12.3%, and 22.8% in Diourbel, Kaolack, and Tambacounda, respectively. Successful sequencing of 121/295 positive samples detected P. falciparum (93%), P. vivax (2.6%), P. malariae (4.4%), and P. ovale wallikeri (0.9%). Plasmodium vivax was co-identified with P. falciparum in thirteen samples. Sequencing also detected two PfHRP2-RDT-negative mono-infections of P. vivax in Tambacounda and Kaolack. CONCLUSION: The findings demonstrate the circulation of P. vivax in western and eastern Senegal, highlighting the need for improved malaria control strategies and accurate diagnostic tools to better understand the prevalence of non-falciparum species countrywide.


Subject(s)
Malaria, Vivax , Plasmodium vivax , Senegal/epidemiology , Humans , Adolescent , Adult , Young Adult , Child , Middle Aged , Male , Female , Plasmodium vivax/genetics , Plasmodium vivax/isolation & purification , Child, Preschool , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Prevalence , Aged , Infant , Polymerase Chain Reaction , Plasmodium ovale/genetics , Plasmodium ovale/isolation & purification
18.
Sci Rep ; 14(1): 9816, 2024 05 02.
Article in English | MEDLINE | ID: mdl-38698102

ABSTRACT

Malaria infection leads to hematological abnormalities, including deranged prothrombin time (PT). Given the inconsistent findings regarding PT in malaria across different severities and between Plasmodium falciparum and P. vivax, this study aimed to synthesize available evidence on PT variations in clinical malaria. A systematic literature search was performed in PubMed, Embase, Scopus, Ovid, and Medline from 27 November 2021 to 2 March 2023 to obtain studies documenting PT in malaria. Study quality was evaluated using the Joanna Briggs Institute checklist, with data synthesized through both qualitative and quantitative methods, including meta-regression and subgroup analyses, to explore heterogeneity and publication bias. From 2767 articles, 21 studies were included. Most studies reported prolonged or increased PT in malaria patients compared to controls, a finding substantiated by the meta-analysis (P < 0.01, Mean difference: 8.86 s, 95% CI 5.32-12.40 s, I2: 87.88%, 4 studies). Severe malaria cases also showed significantly higher PT than non-severe ones (P = 0.03, Hedges's g: 1.65, 95% CI 0.20-3.10, I2: 97.91%, 7 studies). No significant PT difference was observed between P. falciparum and P. vivax infections (P = 0.88, Mean difference: 0.06, 95% CI - 0.691-0.8, I2: 65.09%, 2 studies). The relationship between PT and malaria-related mortality remains unclear, underscoring the need for further studies. PT is typically prolonged or increased in malaria, particularly in severe cases, with no notable difference between P. falciparum and P. vivax infections. The inconsistency in PT findings between fatal and non-fatal cases highlights a gap in current understanding, emphasizing the need for future studies to inform therapeutic strategies.


Subject(s)
Malaria, Falciparum , Malaria, Vivax , Plasmodium falciparum , Plasmodium vivax , Prothrombin Time , Humans , Malaria, Vivax/parasitology , Malaria, Vivax/blood , Malaria, Falciparum/parasitology , Malaria, Falciparum/blood , Plasmodium vivax/pathogenicity , Severity of Illness Index
19.
Malar J ; 23(1): 143, 2024 May 12.
Article in English | MEDLINE | ID: mdl-38735957

ABSTRACT

BACKGROUND: Despite continuous prevention and control strategies in place, malaria remains a major public health problem in sub-Saharan Africa including Ethiopia. Moreover, prevalence of malaria differs in different geographical settings and epidemiological data were inadequate to assure disease status in the study area. This study was aimed to determine the prevalence of malaria and associated risk factors in selected rural kebeles in South Ethiopia. METHODS: A community-based cross-sectional study was conducted between February to June 2019 in eight malaria-endemic kebeles situated in four zones in South Ethiopia. Mult-stage sampling techniques were employed to select the study zones, districts, kebeles and households. Blood sample were collected from 1674 participants in 345 households by finger prick and smears were examined by microscopy. Sociodemographic data as well as risk factors for Plasmodium infection were collected using questionnaires. Bivariate and multivariate logistic regressions were used to analyse the data. RESULTS: The overall prevalence of malaria in the study localities was 4.5% (76/1674). The prevalence was varied among the study localities with high prevalence in Bashilo (14.6%; 33/226) followed by Mehal Korga (12.1%; 26/214). Plasmodium falciparum was the dominant parasite accounted for 65.8% (50/76), while Plasmodium vivax accounted 18.4% (14/76). Co-infection of P. falciparum and P. vivax was 15.8% (12/76). Among the three age groups prevalence was 7.8% (27/346) in age less than 5 years and 7.5% (40/531) in 5-14 years. The age groups > 14years were less likely infected with Plasmodium parasite (AOR = 0.14, 95% CI 0.02-0.82) than under five children. Non-febrile individuals 1638 (97.8%) were more likely to had Plasmodium infection (AOR = 28.4, 95% CI 011.4-70.6) than febrile 36 (2.2%). Individuals living proximity to mosquito breeding sites have higher Plasmodium infection (AOR = 6.17, 95% CI 2.66-14.3) than those at distant of breeding sites. CONCLUSIONS: Malaria remains a public health problem in the study localities. Thus, malaria prevention and control strategies targeting children, non-febrile cases and individuals living proximity to breeding sites are crucial to reduce malaria related morbidity and mortality.


Subject(s)
Family Characteristics , Malaria, Falciparum , Malaria, Vivax , Ethiopia/epidemiology , Cross-Sectional Studies , Prevalence , Humans , Risk Factors , Female , Male , Adolescent , Adult , Child, Preschool , Young Adult , Child , Middle Aged , Infant , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Malaria, Falciparum/epidemiology , Malaria, Falciparum/parasitology , Plasmodium vivax/physiology , Plasmodium falciparum/isolation & purification , Aged , Rural Population/statistics & numerical data , Malaria/epidemiology , Malaria/parasitology
20.
Emerg Infect Dis ; 30(6): 1214-1217, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38662728

ABSTRACT

During May-July 2023, a cluster of 7 patients at local hospitals in Florida, USA, received a diagnosis of Plasmodium vivax malaria. Whole-genome sequencing of the organism from 4 patients and phylogenetic analysis with worldwide representative P. vivax genomes indicated probable single parasite introduction from Central/South America.


Subject(s)
Malaria, Vivax , Phylogeny , Plasmodium vivax , Humans , Malaria, Vivax/epidemiology , Malaria, Vivax/parasitology , Malaria, Vivax/diagnosis , Florida/epidemiology , Plasmodium vivax/genetics , Male , Whole Genome Sequencing , Female , Adult , Middle Aged
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