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BMC Public Health Jul 2023The control of Plasmodium knowlesi malaria remains challenging due to the presence of macaque monkeys and predominantly outdoor-biting Anopheles mosquitoes around human...
Exploring barriers to and facilitators of malaria prevention practices: a photovoice study with rural communities at risk to Plasmodium knowlesi malaria in Sabah, Malaysia.
BACKGROUND
The control of Plasmodium knowlesi malaria remains challenging due to the presence of macaque monkeys and predominantly outdoor-biting Anopheles mosquitoes around human settlements. This study aims to explore the barriers and facilitators related to prevention of mosquito bites among rural communities living in Sabah, Malaysia using the participatory visual method, photovoice.
METHODS
From January through June 2022, 26 participants were recruited from four villages in Kudat, Sabah, using purposive sampling. Participants were male and female villagers, aged > 18 years old. After photovoice training in the villages, participants documented facilitators of and barriers related to avoiding mosquito bites using their own smartphone cameras, and provided narratives for their photos. Twelve Focus Group Discussions (FGDs) sessions in three rounds were held to share and discuss the photos, and to address challenges to the avoidance of mosquito bites. All discussions were conducted in the Sabah Malay dialect, and were video and audio recorded, transcribed, and analyzed using reflexive thematic analysis. The Ideation Model, a meta-theoretical model of behaviour change, underpinned this study.
RESULTS
The most common types of barriers identified by participants included (I) intrapersonal factors such as low perceived threat of malaria, (II) livelihood and lifestyle activities consisting of the local economy and socio-cultural activities, and (III) physical and social environment. The facilitators were categorized into (I) intrapersonal reasons, including having the opportunity to stay indoors, especially women who are housewives, (II) social support by the households, neaighbours and healthcare workers, and (III) support from healthcare services and malaria awareness program. Participants emphasized the importance of stakeholder's support in implementing feasible and affordable approaches to P. knowlesi malaria control.
CONCLUSION
Results provided insights regarding the challenges to preventing P. knowlesi malaria in rural Kudat, Sabah. The participation of communities in research was valuable in expanding knowledge of local challenges and highlighting possible ways to overcome barriers. These findings may be used to improve strategies for zoonotic malaria control, which is critical for advancing social change and minimizing health disparities in malaria prevention.
Topics: Animals; Humans; Female; Male; Adolescent; Malaysia; Rural Population; Insect Bites and Stings; Plasmodium knowlesi; Malaria
PubMed: 37430300
DOI: 10.1186/s12889-023-16173-x -
Tropical Medicine and Infectious Disease Jul 2023The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin , is a promising malaria vaccine candidate....
The cell-traversal protein for ookinetes and sporozoites (CelTOS), expressed on the surface of ookinetes and sporozoitesin , is a promising malaria vaccine candidate. CelTOS is essential for parasite invasion into mosquito midgut and human hepatocytes, thereby contributing to malaria transmission and disease pathogenesis. This study explores the genetic diversity, polymorphisms, haplotypes, natural selection, phylogenetic analysis, and epitope prediction in the full-length gene in clinical samples from Sarawak, Malaysian Borneo, and long-term laboratory strains from Peninsular Malaysia and the Philippines. Our analysis revealed a high level of genetic variation in the gene, with a nucleotide diversity of π ~ 0.021, which was skewed towards the 3' end of the gene. This level of diversity is double that observed in and 20 times that observed in from worldwide clinical samples. Tests of natural selection revealed evidence for positive selection within clinical samples. Phylogenetic analysis of the amino acid sequence of revealed the presence of two distinct groups, although no geographical clustering was observed. Epitope prediction analysis identified two potential epitopes (96AQLKATA102 and 124TIKPPRIKED133) using the IEDB server and one epitope (125IKPPRIKED133) by Bcepred server on the C' terminal region of protein. Both the servers predicted a common epitope region of nine amino acid length (IKPPRIKED) peptide, which can be studied in the future as a potential candidate for vaccine development. These findings shed light on the genetic diversity, polymorphism, haplotypes, and natural selection within in clinical samples and provide insights about its future prospects as a potential candidate for malaria vaccine development.
PubMed: 37624318
DOI: 10.3390/tropicalmed8080380 -
Spatial analyses of Plasmodium knowlesi vectors with reference to control interventions in Malaysia.Parasites & Vectors Oct 2023Malaria parasites such as Plasmodium knowlesi, P. inui, and P. cynomolgi are spread from macaques to humans through the Leucosphyrus Group of Anopheles mosquitoes. It is...
BACKGROUND
Malaria parasites such as Plasmodium knowlesi, P. inui, and P. cynomolgi are spread from macaques to humans through the Leucosphyrus Group of Anopheles mosquitoes. It is crucial to know the distribution of these vectors to implement effective control measures for malaria elimination. Plasmodium knowlesi is the most predominant zoonotic malaria parasite infecting humans in Malaysia.
METHODS
Vector data from various sources were used to create distribution maps from 1957 to 2021. A predictive statistical model utilizing logistic regression was developed using significant environmental factors. Interpolation maps were created using the inverse distance weighted (IDW) method and overlaid with the corresponding environmental variables.
RESULTS
Based on the IDW analysis, high vector abundances were found in the southwestern part of Sarawak, the northern region of Pahang and the northwestern part of Sabah. However, most parts of Johor, Sabah, Perlis, Penang, Kelantan and Terengganu had low vector abundance. The accuracy test indicated that the model predicted sampling and non-sampling areas with 75.3% overall accuracy. The selected environmental variables were entered into the regression model based on their significant values. In addition to the presence of water bodies, elevation, temperature, forest loss and forest cover were included in the final model since these were significantly correlated. Anopheles mosquitoes were mainly distributed in Peninsular Malaysia (Titiwangsa range, central and northern parts), Sabah (Kudat, West Coast, Interior and Tawau division) and Sarawak (Kapit, Miri, and Limbang). The predicted Anopheles mosquito density was lower in the southern part of Peninsular Malaysia, the Sandakan Division of Sabah and the western region of Sarawak.
CONCLUSION
The study offers insight into the distribution of the Leucosphyrus Group of Anopheles mosquitoes in Malaysia. Additionally, the accompanying predictive vector map correlates well with cases of P. knowlesi malaria. This research is crucial in informing and supporting future efforts by healthcare professionals to develop effective malaria control interventions.
Topics: Humans; Animals; Malaysia; Plasmodium knowlesi; Mosquito Vectors; Malaria; Macaca; Anopheles; Spatial Analysis
PubMed: 37814287
DOI: 10.1186/s13071-023-05984-x -
Acta Tropica Dec 2023The 2022 malaria WHO reported around 4000 P. knowlesi infections in the South-East Asia region. In the same period, 72 positive cases were reported by the Department of...
BACKGROUND
The 2022 malaria WHO reported around 4000 P. knowlesi infections in the South-East Asia region. In the same period, 72 positive cases were reported by the Department of Disease Control in Thailand, suggesting a persistent infection. Little is known about dihydrofolate reductase (pkdhfr) and dihydropteroate synthase (pkdhps), putative antimalarial resistance markers for P. knowlesi. The relevant amplification and sequencing protocol are presently unavailable. In this study, we developed a protocol for amplifying and evaluating pkdhps mutations. The haplotype pattern of pkdhfr-pkdhps in Thai isolates was analyzed, and the effects of these pkdhps mutations were predicted by using a computer program.
METHODS
Pkdhps were amplified and sequenced from 28 P. knowlesi samples collected in 2008 and 2020 from nine provinces across Thailand. Combining pkdhfr sequencing data from previous work with pkdhps data to analyze polymorphisms of pkdhfr and pkdhps haplotype. Protein modeling and molecular docking were constructed using two inhibitors, sulfadoxine and sulfamethoxazole, and further details were obtained through analyses of protein-ligand interactions by using the Genetic Optimisation for Ligand Docking program. A phylogenetic tree cluster analysis was reconstructed to compare the P. knowlesi Malaysia isolates.
RESULTS
Five nonsynonymous mutations in the pkdhps were detected outside the equivalence of the binding pocket sites to sulfadoxine and sulfamethoxazole, which are at N391S, E421G, I425R, A449S, and N517S. Based on the modeling and molecular docking analyses, the N391S and N517S mutations located close to the enzyme-binding pocket demonstrated a different docking score and protein-ligand interaction in loop 2 of the enzyme. These findings indicated that it was less likely to induce drug resistance. Of the four haplotypes of pkdhfr-pkdhps, the most common one is the R34L pkdhfr mutation and the pkdhps quadruple mutation (GRSS) at E421G, I425R, A449S, and N517S, which were observed in P. knowlesi in southern Thailand (53.57%). Based on the results of neighbor-joining analysis for pkdhfr and pkdhps, the samples isolated from eastern Thailand displayed a close relationship with Cambodia isolates, while southern Thailand isolates showed a long branch separated from the Malaysian isolates.
CONCLUSIONS
A new PCR protocol amplification and evaluation of dihydropteroate synthase mutations in Knowlesi (pkdhps) has been developed. The most prevalent pkdhfr-pkdhps haplotypes (53.57%) in southern Thailand are R34L pkdhfr mutation and pkdhps quadruple mutation. Further investigation requires additional phenotypic data from clinical isolates, transgenic lines expressing mutant alleles, or recombinant proteins.
Topics: Sulfadoxine; Pyrimethamine; Tetrahydrofolate Dehydrogenase; Dihydropteroate Synthase; Plasmodium knowlesi; Thailand; Molecular Docking Simulation; Ligands; Phylogeny; Antimalarials; Drug Resistance; Sulfamethoxazole; Plasmodium falciparum
PubMed: 37683820
DOI: 10.1016/j.actatropica.2023.107016 -
MedRxiv : the Preprint Server For... Apr 2024Zoonotic and symptomatic and asymptomatic infections occur across endemic areas of Southeast Asia. Most infections are low-parasitemia, with an unknown proportion...
BACKGROUND
Zoonotic and symptomatic and asymptomatic infections occur across endemic areas of Southeast Asia. Most infections are low-parasitemia, with an unknown proportion below routine microscopy detection thresholds. Molecular surveillance tools optimizing the limit of detection (LOD) would allow more accurate estimates of zoonotic malaria prevalence.
METHODS
An established ultra-sensitive genus quantitative-PCR (qPCR) assay targeting the 18S rRNA gene underwent LOD evaluation with and without reverse transcription (RT) for , and using total nucleic acid preserved (DNA/RNA Shield) isolates and archived dried blood spots (DBS). LODs for selected specific assays, and reference and -specific assays were determined with RT. Assay specificities were assessed using clinical malaria samples and malaria-negative controls.
RESULTS
The use of reverse transcription improved species detection by up to 10,000-fold ( genus), 2759-fold (), 1000-fold () and 10-fold (). The median LOD with RT for the Kamau et al. genus RT-qPCR assay was ≤0.0002 parasites/μL for and 0.002 parasites/μL for both and . The LODs with RT for -specific PCRs were: Imwong et al. 18S rRNA (0.0007 parasites/μL); Divis et al. real-time 18S rRNA (0.0002 parasites/μL); Lubis et al. hemi-nested (1.1 parasites/μL) and Lee et al. nested 18S rRNA (11 parasites/μL). The LOD for and specific assays with RT were 0.02 and 0.20 parasites/μL respectively. For DBS samples the median LOD for the genus qPCR with RT was 0.08, and without RT was 19.89 parasites/uL (249-fold change); no LOD improvement was demonstrated in DBS archived beyond 6 years. The genus and -assays were 100% specific for species and detection, respectively, from 190 clinical infections and 48 healthy controls. Reference specific primers demonstrated known cross-reactivity with .
CONCLUSION
Our findings support the use of an 18S rRNA genus qPCR and species-specific nested PCR protocol with RT for highly-sensitive surveillance of zoonotic and human species infections.
PubMed: 38633782
DOI: 10.1101/2024.04.04.24305339 -
Frontiers in Cellular and Infection... 2024, the most widespread human malaria parasite, and , an emerging that infects humans, are the phylogenetically closest malarial species that infect humans, which may...
, the most widespread human malaria parasite, and , an emerging that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage and parasites and ascertain their cross-species immunoreactivity. Recombinant and MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with or infections. The MTRAPs of (PvMTRAP) and (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with . MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria.
Topics: Animals; Humans; Plasmodium vivax; Parasites; Merozoites; Thrombospondins; Plasmodium; Malaria; Malaria, Vivax; Protozoan Proteins; Mammals
PubMed: 38465236
DOI: 10.3389/fcimb.2024.1354880 -
Journal of Vector Borne Diseases 2023Severe malaria is a medical emergency and can lead to severe complications and death if not treated promptly and appropriately. Along with Plasmodium falciparum, P....
BACKGROUND & OBJECTIVES
Severe malaria is a medical emergency and can lead to severe complications and death if not treated promptly and appropriately. Along with Plasmodium falciparum, P. knowlesi is increasingly recognised as a significant cause of fatal and severe malaria.
METHODS
We performed a retrospective review on 54 cases of severe malaria in a district hospital in Kapit, Sarawak, from January 2018 to May 2019. The patients' demographics, clinical features, complications based on organ involvement, and treatment outcomes were examined.
RESULTS
There were 54 cases of severe malaria, with the majority being male (70%) and between the ages of 40 and 49 (26%). All patients with severe malaria were febrile or had a history of pyrexia except for one patient. P. knowlesi (81.5%) was the most common species causing severe malaria in our study, followed by P. falciparum (13%), and P. vivax (5.5%). There were no cases of severe malaria caused by P. ovale or P. malariae. Hyperparasitaemia was present in 76% of patients and the median parasitemia value at hospital admission was 33,944 parasites/μL (interquartile range: 19,920-113,285 parasites/μL). Circulatory shock was observed in 17 patients (31.5%). There were eight patients with acute renal failure and six patients with respiratory distress. One patient died as a result of severe malaria with multiorgan involvement (1.9% fatality rate).
INTERPRETATION & CONCLUSION
P. knowlesi is the most common cause of severe malaria in Kapit, Sarawak, Malaysia. Recognizing symptoms of severe malaria and prompt administration of antimalarial are critical for good clinical outcomes.
Topics: Humans; Male; Adult; Middle Aged; Female; Malaysia; Borneo; Plasmodium knowlesi; Malaria; Antimalarials; Malaria, Vivax; Malaria, Falciparum
PubMed: 38174522
DOI: 10.4103/0972-9062.374238 -
Comparative Medicine Jun 2024Malaria is a parasitic disease caused by protozoan species of the genus and transmitted by female mosquitos of the genus and other Culicidae. Most of the parasites of...
Malaria is a parasitic disease caused by protozoan species of the genus and transmitted by female mosquitos of the genus and other Culicidae. Most of the parasites of the genus are highly species specific with more than 200 species described affecting different species of mammals, birds, and reptiles. species strictly affecting humans are , , , and More recently, and other nonhuman primate plasmodia were found to naturally infect humans. Currently, malaria occurs mostly in poor tropical and subtropical areas of the world, and in many of these countries it is the leading cause of illness and death. For more than 100 y, animal models, have played a major role in our understanding of malaria biology. Avian species were the first to be used as models to study human malaria. Malaria parasite biology and immunity were first studied using mainly and . Rodent malarias, particularly and , have been used extensively as models to study malaria in mammals. Several species of from nonhuman primates have been used as surrogate models to study human malaria immunology, pathogenesis, candidate vaccines, and treatments. , , and are important models for studying malaria produced by and , while is used as a model for studying severe malaria. Other nonhuman primate malarias used in research are , , , , and . Very few nonhuman primate species can develop an infection with human malarias. Macaques in general are resistant to infection with , , , and . Only apes and a few species of New World monkeys can support infection with human malarias. Herein we review the most common, and some less common, avian, reptile, and mammal plasmodia species used as models to study human malaria.
PubMed: 38902006
DOI: 10.30802/AALAS-CM-24-000019 -
MedRxiv : the Preprint Server For... Aug 2023is a zoonotic parasite that causes malaria in humans. The pathogen has a natural host reservoir in certain macaque species and is transmitted to humans via mosquitoes...
BACKGROUND
is a zoonotic parasite that causes malaria in humans. The pathogen has a natural host reservoir in certain macaque species and is transmitted to humans via mosquitoes of the Leucosphyrus Group. The risk of human infection varies across Southeast Asia and is dependent upon environmental factors. Understanding this geographic variation in risk is important both for enabling appropriate diagnosis and treatment of the disease and for improving the planning and evaluation of malaria elimination. However, the data available on occurrence are biased towards regions with greater surveillance and sampling effort. Predicting the spatial variation in risk of malaria requires methods that can both incorporate environmental risk factors and account for spatial bias in detection.
METHODS & RESULTS
We extend and apply an environmental niche modelling framework as implemented by a previous mapping study of transmission risk which included data up to 2015. We reviewed the literature from October 2015 through to March 2020 and identified 264 new records of , with a total of 524 occurrences included in the current study following consolidation with the 2015 study. The modelling framework used in the 2015 study was extended, with changes including the addition of new covariates to capture the effect of deforestation and urbanisation on transmission.
DISCUSSION
Our map of relative transmission suitability estimates that the risk posed by the pathogen is highest in Malaysia and Indonesia, with localised areas of high risk also predicted in the Greater Mekong Subregion, The Philippines and Northeast India. These results highlight areas of priority for surveillance and prospective sampling to address the challenge the disease poses to malaria elimination planning.
PubMed: 37609228
DOI: 10.1101/2023.08.04.23293633 -
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