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Genome Medicine Nov 2023Malaria continues to be a major threat to global public health. Whole genome sequencing (WGS) of the underlying Plasmodium parasites has provided insights into the...
BACKGROUND
Malaria continues to be a major threat to global public health. Whole genome sequencing (WGS) of the underlying Plasmodium parasites has provided insights into the genomic epidemiology of malaria. Genome sequencing is rapidly gaining traction as a diagnostic and surveillance tool for clinical settings, where the profiling of co-infections, identification of imported malaria parasites, and detection of drug resistance are crucial for infection control and disease elimination. To support this informatically, we have developed the Malaria-Profiler tool, which rapidly (within minutes) predicts Plasmodium species, geographical source, and resistance to antimalarial drugs directly from WGS data.
RESULTS
The online and command line versions of Malaria-Profiler detect ~ 250 markers from genome sequences covering Plasmodium speciation, likely geographical source, and resistance to chloroquine, sulfadoxine-pyrimethamine (SP), and other anti-malarial drugs for P. falciparum, but also providing mutations for orthologous resistance genes in other species. The predictive performance of the mutation library was assessed using 9321 clinical isolates with WGS and geographical data, with most being single-species infections (P. falciparum 7152/7462, P. vivax 1502/1661, P. knowlesi 143/151, P. malariae 18/18, P. ovale ssp. 5/5), but co-infections were identified (456/9321; 4.8%). The accuracy of the predicted geographical profiles was high to both continental (96.1%) and regional levels (94.6%). For P. falciparum, markers were identified for resistance to chloroquine (49.2%; regional range: 24.5% to 100%), sulfadoxine (83.3%; 35.4- 90.5%), pyrimethamine (85.4%; 80.0-100%) and combined SP (77.4%). Markers associated with the partial resistance of artemisinin were found in WGS from isolates sourced from Southeast Asia (30.6%).
CONCLUSIONS
Malaria-Profiler is a user-friendly tool that can rapidly and accurately predict the geographical regional source and anti-malarial drug resistance profiles across large numbers of samples with WGS data. The software is flexible with modifiable bioinformatic pipelines. For example, it is possible to select the sequencing platform, display specific variants, and customise the format of outputs. With the increasing application of next-generation sequencing platforms on Plasmodium DNA, Malaria-Profiler has the potential to be integrated into point-of-care and surveillance settings, thereby assisting malaria control. Malaria-Profiler is available online (bioinformatics.lshtm.ac.uk/malaria-profiler) and as standalone software ( https://github.com/jodyphelan/malaria-profiler ).
Topics: Humans; Animals; Antimalarials; Parasites; Coinfection; Malaria; Plasmodium; Malaria, Falciparum; Chloroquine; Malaria, Vivax; Drug Resistance; Plasmodium falciparum
PubMed: 37950308
DOI: 10.1186/s13073-023-01247-7 -
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 -
Open Forum Infectious Diseases Nov 2023Scarcity of annotated image data sets of thin blood smears makes expert-level differentiation among species challenging. Here, we aimed to establish a deep learning...
BACKGROUND
Scarcity of annotated image data sets of thin blood smears makes expert-level differentiation among species challenging. Here, we aimed to establish a deep learning algorithm for identifying and classifying malaria parasites in thin blood smears and evaluate its performance and clinical prospect.
METHODS
You Only Look Once v7 was used as the backbone network for training the artificial intelligence algorithm model. The training, validation, and test sets for each malaria parasite category were randomly selected. A comprehensive analysis was performed on 12 708 thin blood smear images of various infective stages of 12 546 malaria parasites, including , , , , , and . Peripheral blood samples were obtained from 380 patients diagnosed with malaria. Additionally, blood samples from monkeys diagnosed with malaria were used to analyze . The accuracy for detecting -infected blood cells was assessed through various evaluation metrics.
RESULTS
The total time to identify 1116 malaria parasites was 13 seconds, with an average analysis time of 0.01 seconds for each parasite in the test set. The average precision was 0.902, with a recall and precision of infected erythrocytes of 96.0% and 94.9%, respectively. Sensitivity and specificity exceeded 96.8% and 99.3%, with an area under the receiver operating characteristic curve >0.999. The highest sensitivity (97.8%) and specificity (99.8%) were observed for trophozoites and merozoites.
CONCLUSIONS
The algorithm can help facilitate the clinical and morphologic examination of malaria parasites.
PubMed: 37937045
DOI: 10.1093/ofid/ofad469 -
Parasitology Nov 2023Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously... (Review)
Review
Of the 5 human malarial parasites, and are the most prevalent species globally, while and are less prevalent and typically occur as mixed-infections. , previously considered a non-human primate (NHP) infecting species, is now a cause of human malaria in Malaysia. The other NHP species, , , , , and cause malaria in primates, which are mainly reported in southeast Asia and South America. The non- NHP species also emerged and were found to cross-transmit from their natural hosts (NHP) – to human hosts in natural settings. Here we have reviewed and collated data from the literature on the NHPs-to-human-transmitting species. It was observed that the natural transmission of these NHP parasites to humans had been reported from 2010 onwards. This study shows that: (1) the majority of the non- NHP mixed species infecting human cases were from Yala province of Thailand; (2) mono/mixed infections with other human-infecting species were prevalent in Malaysia and Thailand and (3) and were found in Central and South America.
Topics: Animals; Humans; Malaria; Plasmodium knowlesi; Primates; Asia, Southeastern; Plasmodium vivax
PubMed: 37929579
DOI: 10.1017/S003118202300077X -
Frontiers in Public Health 2023In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data... (Review)
Review
INTRODUCTION
In 2021, India contributed for ~79% of malaria cases and ~ 83% of deaths in the South East Asia region. Here, we systematically and critically analyzed data published on malaria in pregnancy (MiP) in India.
METHODS
Epidemiological, clinical, parasitological, preventive and therapeutic aspects of MiP and its consequences on both mother and child were reviewed and critically analyzed. Knowledge gaps and solution ways are also presented and discussed. Several electronic databases including Google scholar, Google, PubMed, Scopus, Wiley Online library, the Malaria in Pregnancy Consortium library, the World Malaria Report, The WHO regional websites, and ClinicalTrials.gov were used to identify articles dealing with MiP in India. The archives of local scientific associations/journals and website of national programs were also consulted.
RESULTS
Malaria in pregnancy is mainly due to () and (), and on rare occasions to spp. and too. The overall prevalence of MiP is ~0.1-57.7% for peripheral malaria and ~ 0-29.3% for placental malaria. Peripheral infection at antenatal care (ANC) visits decreased from ~13% in 1991 to ~7% in 1995-1996 in Madhya Pradesh, while placental infection at delivery unit slightly decreased from ~1.5% in 2006-2007 to ~1% in 2012-2015 in Jharkhand. In contrast, the prevalence of peripheral infection at ANC increased from ~1% in 2006-2007 to ~5% in 2015 in Jharkhand, and from ~0.5% in 1984-1985 to ~1.5% in 2007-2008 in Chhattisgarh. Clinical presentation of MiP is diverse ranging from asymptomatic carriage of parasites to severe malaria, and associated with comorbidities and concurrent infections such as malnutrition, COVID-19, dengue, and cardiovascular disorders. Severe anemia, cerebral malaria, severe thrombocytopenia, and hypoglycemia are commonly seen in severe MiP, and are strongly associated with tragic consequences such as abortion and stillbirth. Congenital malaria is seen at prevalence of ~0-12.9%. Infected babies are generally small-for-gestational age, premature with low birthweight, and suffer mainly from anemia, thrombocytopenia, leucopenia and clinical jaundice. Main challenges and knowledge gaps to MiP control included diagnosis, relapsing malaria, mixed infection treatment, self-medication, low density infections and utility of artemisinin-based combination therapies.
CONCLUSION
All taken together, the findings could be immensely helpful to control MiP in malaria endemic areas.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Abortion, Spontaneous; Anemia; India; Malaria; Malaria, Vivax; Placenta; Thrombocytopenia
PubMed: 37927870
DOI: 10.3389/fpubh.2023.1150466 -
Microorganisms Sep 2023Here, the main goal is to assess natural infections of spp. in anophelines in a forest reserve from the same region where we previously found a surprisingly high rate...
Here, the main goal is to assess natural infections of spp. in anophelines in a forest reserve from the same region where we previously found a surprisingly high rate (5.2%) of plasmodia infections ( = 25) in mosquitoes ( = 480) on the slopes of Serra do Mar, Atlantic Forest, Brazil. The mosquito collection sampling was carried out at the Legado das Águas Forest Reserve using CDC light traps and Shannon traps at night (5-10 pm) in 3-day collections in November 2021 and March, April, May, and November 2022. The captured specimens were morphologically identified at the species level and had their genomic DNA extracted in pools of up to 10 mosquitoes/pool. Each pool was tested using qPCR and nested PCR plus sequencing. A total of 5301 mosquitoes, mostly belonging to the genus (99.7%), were sampled and sorted into 773 pools. Eight pools positive for spp. were identified: four for spp., one for or , one for or , and two for the -like parasite. After Sanger sequencing, two results were further confirmed: or and or . The minimum infection rate for mosquitoes was 0.15% (eight positive pools/5285 mosquitoes). The study reveals a lower-than-expected natural infection rate (expected = 5.2% vs. observed = 0.15%). This low rate relates to the absence of monkeys as the main simian malaria reservoir in the studied region. Their absence was due to a significant population decline following the reemergence of yellow fever virus outbreaks in the Atlantic Forest from 2016 to 2019. However, this also indicates the existence of alternative reservoirs to infect mosquitoes. The found zoonotic species of , including the . -like parasite, may represent a simian malaria risk and thus a challenge for malaria elimination in Brazil.
PubMed: 37894123
DOI: 10.3390/microorganisms11102465 -
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 -
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 -
Tropical Parasitology 2023Nonhuman primate (NHP) malaria poses a major threat to the malaria control programs. The last two decades have witnessed a paradigm shift in our understanding of the... (Review)
Review
Nonhuman primate (NHP) malaria poses a major threat to the malaria control programs. The last two decades have witnessed a paradigm shift in our understanding of the malaria caused by species other than the traditionally known human species - , , , and . The emergence of the malaria parasite of long-tailed macaque monkeys, , as the fifth malaria species of humans has made the scientific community consider the risk of other zoonotic malaria, such as , , , and others, to humans. The development of knowledge about as a pathogen which was earlier only known to experimentally cause malaria in humans and rarely cause natural infection, toward its acknowledgment as a significant cause of human malaria and a threat of malaria control programs has been made possible by the use of advanced molecular techniques such as polymerase chain reaction and gene sequencing. This review explores the various aspects of NHP malaria, and the association of various factors with their emergence and potential to cause human malaria which are important to understand to be able to control these emerging infections.
PubMed: 37860614
DOI: 10.4103/tp.tp_79_22 -
Nature Communications Oct 2023Reports suggest non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa but their epidemiology is ill-defined, particularly in highly...
Reports suggest non-falciparum species are an underappreciated cause of malaria in sub-Saharan Africa but their epidemiology is ill-defined, particularly in highly malaria-endemic regions. We estimated incidence and prevalence of PCR-confirmed non-falciparum and Plasmodium falciparum malaria infections within a longitudinal study conducted in Kinshasa, Democratic Republic of Congo (DRC) between 2015-2017. Children and adults were sampled at biannual household surveys and routine clinic visits. Among 9,089 samples from 1,565 participants, incidences of P. malariae, P. ovale spp., and P. falciparum infections by 1-year were 7.8% (95% CI: 6.4%-9.1%), 4.8% (95% CI: 3.7%-5.9%) and 57.5% (95% CI: 54.4%-60.5%), respectively. Non-falciparum prevalences were higher in school-age children, rural and peri-urban sites, and P. falciparum co-infections. P. falciparum remains the primary driver of malaria in the DRC, though non-falciparum species also pose an infection risk. As P. falciparum interventions gain traction in high-burden settings, continued surveillance and improved understanding of non-falciparum infections are warranted.
Topics: Child; Adult; Humans; Plasmodium ovale; Plasmodium malariae; Democratic Republic of the Congo; Longitudinal Studies; Malaria, Falciparum; Malaria; Prevalence; Plasmodium falciparum
PubMed: 37857597
DOI: 10.1038/s41467-023-42190-w