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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 -
Antimicrobial Agents and Chemotherapy Dec 2023Malaria molecular surveillance remains critical in detecting and tracking emerging parasite resistance to anti-malarial drugs. The current study employed molecular...
Malaria molecular surveillance remains critical in detecting and tracking emerging parasite resistance to anti-malarial drugs. The current study employed molecular techniques to determine species prevalence and characterize the genetic diversity of and molecular markers of sulfadoxine-pyrimethamine resistance in humans and wild mosquito populations in Cameroon. mosquito collections and parasitological survey were conducted in villages to determine species infection, and genomic phenotyping of anti-folate resistance was accomplished by sequencing the dihydrofolate-reductase () and dihydropteroate-synthase () genes of naturally circulating and isolates. The malaria prevalence in Elende was 73.5% with the 5-15 years age group harboring significant (27%) and (19%) infections. The polymorphism breadth of the pyrimethamine-associated marker revealed a near fixation (94%) of the triple-mutant -AI. The backbone mediating sulfadoxine resistance reveals a high frequency of the KAA alleles (20.8%). Similarly, the NKSSFI haplotype (78.4%) was predominantly detected in the asexual blood stage. In contrast, the - occured at 37.2% frequency. The combined quadruple NKSSFI_ KAA (31.9%) was the major circulating haplotype with similar frequency in humans and mosquitoes. This study highlights the increasing frequency of the parasite mostly common in asymptomatic individuals with apparent infection. Interventions directed at reducing malaria transmission such as the scaling-up of SP are favoring the emergence and spread of multiple drug-resistant alleles between the human and mosquito host systems.
Topics: Animals; Humans; Pyrimethamine; Sulfadoxine; Anopheles; Alleles; Cameroon; Antimalarials; Malaria, Falciparum; Drug Combinations; Plasmodium falciparum; Malaria; Drug Resistance; Tetrahydrofolate Dehydrogenase
PubMed: 37947766
DOI: 10.1128/aac.00588-23 -
Infectious Diseases of Poverty Nov 2023Plasmodium malariae was always neglected compared with P. falciparum and P. vivax. In the present study, we aimed to describe the epidemiology of reported cases infected...
BACKGROUND
Plasmodium malariae was always neglected compared with P. falciparum and P. vivax. In the present study, we aimed to describe the epidemiology of reported cases infected with P. malariae in the past decade to raise awareness of the potential threat of this malaria parasite in China.
METHODS
Individual data of malaria cases infected with P. malariae reported in China in the past decade were collected via the China Information System for Disease Control and Prevention and Parasitic Diseases Information Reporting Management System, to explore their epidemiological characteristics. Pearson Chi-square tests or Fisher's Exact Test was used in the statistical analysis.
RESULTS
From 2013 to 2022, a total of 581 P. malariae cases were reported in China, and mainly concentrated in 20-59 years old group (P < 0.001), and there was no significant trend in the number of cases reported per month. Moreover, four kinds of P. malariae cases were classified, including 567 imported cases from 41 countries in 8 regions and distributed in 27 provinces (autonomous regions, municipalities) in China, six indigenous cases in a small outbreak in Hainan, seven recurrent cases in Guangdong and Shanghai, and one induced case in Shanghai, respectively. In addition, only 379 cases (65.2%) were diagnosed as malaria on the first visit (P < 0.001), and 413 cases (71.1%) were further confirmed as P. malariae cases (P = 0.002). Meanwhile, most cases sought healthcare first in the health facilities at the county and prefectural levels, but only 76.7% (161/210) and 73.7% (146/198) cases were diagnosed as malaria, and the accuracy of confirmed diagnosis as malaria cases infected with P. malariae was only 77.2% (156/202) and 69.9% (167/239) in these health facilities respectively.
CONCLUSIONS
Even though malaria cases infected with P. malariae didn't account for a high proportion of reported malaria cases nationwide, the threat posed by widely distributed imported cases, a small number of indigenous cases, recurrent cases and induced case cannot be ignored in China. Therefore, it is necessary to raise awareness and improve the surveillance and response to the non-falciparum species such as P. malariae, and prevent the reestablishment of malaria transmission after elimination.
Topics: Humans; Young Adult; Adult; Middle Aged; Plasmodium malariae; China; Malaria; Malaria, Falciparum; Malaria, Vivax
PubMed: 37986018
DOI: 10.1186/s40249-023-01156-2 -
Transfusion Jan 2024Malaria is caused by protozoa of the genus Plasmodium and transmitted by Anopheles mosquitos. In the US, blood donors are assessed for malaria risk, including donor...
BACKGROUND
Malaria is caused by protozoa of the genus Plasmodium and transmitted by Anopheles mosquitos. In the US, blood donors are assessed for malaria risk, including donor travel or previous residence in endemic areas and history of malaria by questionnaire and deferred for three months or three years, respectively.
METHODS
The Procleix Plasmodium Assay is a qualitative nucleic acid test based on transcription-mediated amplification (TMA) for the detection of 18S ribosomal RNA of P. falciparum, P. ovale, P. vivax, P. malariae, and P. knowlesi for use on the Procleix Panther system. Analytical sensitivity was evaluated with in vitro transcripts and infected red blood cells. For clinical specificity, 12,800 individual donations and 283 pools of 16 samples from routine US donors were screened. Malaria risk was evaluated by testing 862 donors deferred for 3 years. Reactive results were confirmed with in-house real-time TMA assay and serology.
RESULTS
Assay sensitivity was 8.47-11.89 RNA copies/mL and 2.10-6.82 infected red cells/mL. Specificity was 99.99% in 12,800 individual donations and 100% in 283 pools of 16. Of 862 tested deferred donor samples, one donor (0.12%) confirmed positive individually and in pools; he remained confirmed positive for 13 months. The infected donor was a prior resident of a malaria-endemic area in West Africa.
CONCLUSIONS
The Procleix Plasmodium Assay showed high sensitivity and specificity and detected Plasmodium RNA in an asymptomatic presenting donor. This assay may prove helpful as a screening test versus the use of risk questions to reduce the number of donors deferred for malaria risk.
Topics: Animals; Humans; Male; Blood Transfusion; Malaria; Malaria, Falciparum; Plasmodium; RNA
PubMed: 38018462
DOI: 10.1111/trf.17612 -
Micromachines Oct 2023Malaria is listed as one of the three most hazardous infectious diseases worldwide. Travelers and migrants passing through exit and entry ports are important sources of...
Malaria is listed as one of the three most hazardous infectious diseases worldwide. Travelers and migrants passing through exit and entry ports are important sources of malaria pandemics globally. Developing accurate and rapid detection technology for malaria is important. Here, a novel hairpin-mediated amplification (HMA) technique was proposed for the detection of four Plasmodium species, including , , , and . Based on the conserved nucleotide sequence of Plasmodium, specific primers and probes were designed for the HMA process, and the amplicon can be detected using lateral flow detection (LFD); the results can be read visually without specialized equipment. The specificity of HMA-LFD was evaluated using nucleic acids extracted from four different Plasmodium species and two virus species. The sensitivity of HMA-LFD was valued using 10× serial dilutions of plasmid containing the template sequence. Moreover, 78 blood samples were collected to compare HMA-LFD and qPCR. The HMA-LFD results were all positive for four different Plasmodium species and negative for the other two virus species. The sensitivity of HMA-LFD was tested to be near five copies/μL. The analysis of clinical samples indicated that the consistency of HMA-LFD and qPCR was approximately 96.15%. Based on these results, the HMA-LFD assay was demonstrated to be a rapid, sensitive, and specific technique for the detection of Plasmodium and has great advantages for on-site detection in low-resource areas and exit and entry ports.
PubMed: 37893354
DOI: 10.3390/mi14101917 -
Journal of Travel Medicine Apr 2024Malaria continues to pose a significant burden in endemic countries, many of which lack access to molecular surveillance. Insights from malaria cases in travellers...
BACKGROUND
Malaria continues to pose a significant burden in endemic countries, many of which lack access to molecular surveillance. Insights from malaria cases in travellers returning to non-endemic areas can provide valuable data to inform endemic country programmes. To evaluate the potential for novel global insights into malaria, we examined epidemiological and molecular data from imported malaria cases to Australia.
METHODS
We analysed malaria cases reported in Australia from 2012 to 2022 using National Notifiable Disease Surveillance System data. Molecular data on imported malaria cases were obtained from literature searches.
RESULTS
Between 2012 and 2022, 3204 malaria cases were reported in Australia. Most cases (69%) were male and 44% occurred in young adults aged 20-39 years. Incidence rates initially declined between 2012 and 2015, then increased until 2019. During 2012-2019, the incidence in travellers ranged from 1.34 to 7.71 per 100 000 trips. Cases were primarily acquired in Sub-Saharan Africa (n = 1433; 45%), Oceania (n = 569; 18%) and Southern and Central Asia (n = 367; 12%). The most common countries of acquisition were Papua New Guinea (n = 474) and India (n = 277). Plasmodium falciparum accounted for 58% (1871/3204) of cases and was predominantly acquired in Sub-Saharan Africa, and Plasmodium vivax accounted for 32% (1016/3204), predominantly from Oceania and Asia. Molecular studies of imported malaria cases to Australia identified genetic mutations and deletions associated with drug resistance and false-negative rapid diagnostic test results, and led to the establishment of reference genomes for P. vivax and Plasmodium malariae.
CONCLUSIONS
Our analysis highlights the continuing burden of imported malaria into Australia. Molecular studies have offered valuable insights into drug resistance and diagnostic limitations, and established reference genomes. Integrating molecular data into national surveillance systems could provide important infectious disease intelligence to optimize treatment guidelines for returning travellers and support endemic country surveillance programmes.
Topics: Young Adult; Male; Humans; Female; Travel; Malaria; Malaria, Vivax; Plasmodium falciparum; Australia
PubMed: 38127641
DOI: 10.1093/jtm/taad164 -
Malaria Journal Sep 2023The routine surveillance of asymptomatic malaria using nucleic acid-based amplification tests is essential in obtaining reliable data that would inform malaria policy...
BACKGROUND
The routine surveillance of asymptomatic malaria using nucleic acid-based amplification tests is essential in obtaining reliable data that would inform malaria policy formulation and the implementation of appropriate control measures.
METHODS
In this study, the prevalence rate and the dynamics of Plasmodium species among asymptomatic children (n = 1697) under 5 years from 30 communities within the Hohoe municipality in Ghana were determined.
RESULTS AND DISCUSSION
The observed prevalence of Plasmodium parasite infection by polymerase chain reaction (PCR) was 33.6% (571/1697), which was significantly higher compared to that obtained by microscopy [26.6% (451/1697)] (P < 0.0001). Based on species-specific analysis by nested PCR, Plasmodium falciparum infection [33.6% (570/1697)] was dominant, with Plasmodium malariae, Plasmodium ovale and Plasmodium vivax infections accounting for 0.1% (1/1697), 0.0% (0/1697), and 0.0% (0/1697), respectively. The prevalence of P. falciparum infection among the 30 communities ranged from 0.0 to 82.5%. Following artesunate-amodiaquine (AS + AQ, 25 mg/kg) treatment of a sub-population of the participants (n = 184), there was a substantial reduction in Plasmodium parasite prevalence by 100% and 79.2% on day 7 based on microscopy and nested PCR analysis, respectively. However, there was an increase in parasite prevalence from day 14 to day 42, with a subsequent decline on day 70 by both microscopy and nested PCR. For parasite clearance rate analysis, we found a significant proportion of the participants harbouring residual Plasmodium parasites or parasite genomic DNA on day 1 [65.0% (13/20)], day 2 [65.0% (13/20)] and day 3 [60.0% (12/20)] after initiating treatment. Of note, gametocyte carriage among participants was low before and after treatment.
CONCLUSION
Taken together, the results indicate that a significant number of individuals could harbour residual Plasmodium parasites or parasite genomic DNA after treatment. The study demonstrates the importance of routine surveillance of asymptomatic malaria using sensitive nucleic acid-based amplification techniques.
Topics: Child; Humans; Ghana; Malaria; Artemisinins; Malaria, Falciparum; Plasmodium malariae; Nucleic Acids
PubMed: 37710288
DOI: 10.1186/s12936-023-04712-1 -
Tropical Medicine and Infectious Disease Sep 2023Up-to-date knowledge of key epidemiological aspects of each species is necessary for making informed decisions on targeted interventions and control strategies to...
Up-to-date knowledge of key epidemiological aspects of each species is necessary for making informed decisions on targeted interventions and control strategies to eliminate each of them. This study aims to describe the epidemiology of plasmodial species in Mali, where malaria is hyperendemic and seasonal. Data reports collected during high-transmission season over six consecutive years were analyzed to summarize malaria epidemiology. Malaria species and density were from blood smear microscopy. Data from 6870 symptomatic and 1740 asymptomatic participants were analyzed. The median age of participants was 12 years, and the sex ratio (male/female) was 0.81. Malaria prevalence from all species was 65.20% (95% CI: 60.10-69.89%) and 22.41% (CI: 16.60-28.79%) for passive and active screening, respectively. was the most prevalent species encountered in active and passive screening (59.33%, 19.31%). This prevalence was followed by (1.50%, 1.15%) and (0.32%, 0.06%). Regarding frequency, was more frequent in symptomatic individuals (96.77% vs. 93.24%, = 0.014). In contrast, was more frequent in asymptomatic individuals (5.64% vs. 2.45%, < 0.001). remained the least frequent species (less than 1%), and no was detected. The most frequent coinfections were and (0.56%). Children aged 5-9 presented the highest frequency of infections (41.91%). Non- species were primarily detected in adolescents (10-14 years) with frequencies above 50%. Only infections had parasitemias greater than 100,000 parasites per µL of blood. gametocytes were found with variable prevalence across age groups. Our data highlight that represented the first burden, but other non- species were also important. Increasing attention to and is essential if malaria elimination is to be achieved.
PubMed: 37755899
DOI: 10.3390/tropicalmed8090438 -
Tropical Medicine and Infectious Disease Oct 2023() causes zoonotic malaria and is known as the "fifth human malaria parasite". malaria is an emerging threat because infections are increasing and can be fatal. While... (Review)
Review
() causes zoonotic malaria and is known as the "fifth human malaria parasite". malaria is an emerging threat because infections are increasing and can be fatal. While most infections are in Southeast Asia (SEA), especially Malaysia, travelers frequently visit this region and can present with malaria around the world. So, clinicians need to know (1) patients who present with fever after recent travel to SEA might be infected with and (2) is often misdiagnosed as (which typically causes less severe malaria). Here we review the history, pathophysiology, clinical features, diagnosis, and treatment of malaria. Severe disease is most common in adults. Signs and symptoms can include fever, abdominal pain, jaundice, acute kidney injury, acute respiratory distress syndrome, hyponatremia, hyperparasitemia, and thrombocytopenia. Dengue is one of the diseases to be considered in the differential. Regarding pathophysiologic mechanisms, when parasites invade mature red blood cells (RBCs, i.e., normocytes) and reticulocytes, changes in the red blood cell (RBC) surface can result in life-threatening cytoadherence, sequestration, and reduced RBC deformability. Since molecular mechanisms involving the erythrocytic stage are responsible for onset of severe disease and lethal outcomes, it is biologically plausible that manual exchange transfusion (ET) or automated RBC exchange (RBCX) could be highly beneficial by replacing "sticky" parasitized RBCs with uninfected, deformable, healthy donor RBCs. Here we suggest use of special -resistant donor RBCs to optimize adjunctive manual ET/RBCX for malaria. "Therapeutically-rational exchange transfusion" (T-REX) is proposed in which -resistant RBCs are transfused (instead of disease-promoting RBCs). Because expression of the Duffy antigen on the surface of human RBCs is essential for parasite invasion, T-REX of Duffy-negative RBCs-also known as Fy(a-b-) RBCs-could replace the majority of the patient's circulating normocytes with invasion-resistant RBCs (in a single procedure lasting about 2 h). When sequestered or non-sequestered iRBCs rupture-in a 24 h asexual life cycle-the released merozoites cannot invade Fy(a-b-) RBCs. When Fy(a-b-) RBC units are scarce (e.g., in Malaysia), clinicians can consider the risks and benefits of transfusing plausibly -resistant RBCs, such as glucose-6-phosphate dehydrogenase deficient (G6PDd) RBCs and Southeast Asian ovalocytes (SAO). Patients typically require a very short recovery time (<1 h) after the procedure. Fy(a-b-) RBCs should have a normal lifespan, while SAO and G6PDd RBCs may have mildly reduced half-lives. Because SAO and G6PDd RBCs come from screened blood donors who are healthy and not anemic, these RBCs have a low-risk for hemolysis and do not need to be removed after the patient recovers from malaria. T-REX could be especially useful if (1) antimalarial medications are not readily available, (2) patients are likely to progress to severe disease, or (3) drug-resistant strains emerge. In conclusion, T-REX is a proposed optimization of manual ET/RBCX that has not yet been utilized but can be considered by physicians to treat malaria patients.
PubMed: 37888606
DOI: 10.3390/tropicalmed8100478 -
Parasitology Research Jul 2023Due to the increasing number of returnees from malaria endemic areas, imported malaria has become a public health challenge in China. To better understand the...
Due to the increasing number of returnees from malaria endemic areas, imported malaria has become a public health challenge in China. To better understand the characteristics of imported Plasmodium species and adjust appropriate strategies for malaria prevention and control in Eastern China, we conducted molecular detection and species identification on 1282 imported malaria cases in Shandong Province between 2012 and 2018. The findings showed that P. falciparum was predominant, particularly in cases imported from Africa. P. vivax was the dominant species imported from Asian countries. Additionally, imported P. ovale and P. malariae emerged in the province. Further surveillance and control of imported malaria among returnees from Africa and Southeast Asia is needed to be strengthened in Eastern China.
Topics: Humans; Malaria; Plasmodium; Africa; China; Malaria, Falciparum; Malaria, Vivax
PubMed: 37199766
DOI: 10.1007/s00436-023-07865-9