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Tropical Medicine and Infectious Disease Jan 2023has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages...
has emerged as an important zoonotic parasite that causes persistent symptomatic malaria in humans. The signs and symptoms of malaria are attributed to the blood stages of the parasites, which start from the invasion of erythrocytes by the blood stage merozoites. The apical membrane protein 1 (AMA-1) plays an important role in the invasion. In this study, we constructed and expressed recombinant PkAMA-1 domain II (PkAMA-1-DII) representing the predominant haplotypes from Peninsular Malaysia and Malaysian Borneo and raised specific antibodies against the recombinant proteins in rabbits. Despite the minor amino acid sequence variation, antibodies raised against haplotypes from Peninsular Malaysia and Malaysian Borneo demonstrated different invasion inhibition (46.81% and 39.45%, respectively) to A1-H.1, a reference strain derived from Peninsular Malaysia. Here, we demonstrated how a minor variation in a conserved parasite protein could cast a significant impact on parasite invasion biology, suggesting a complex host-switching of from different locations. This may challenge the implementation of a standardized One Health approach against the transmission of knowlesi malaria.
PubMed: 36668963
DOI: 10.3390/tropicalmed8010056 -
Parasites & Vectors Jan 2023
PubMed: 36627715
DOI: 10.1186/s13071-022-05631-x -
The Korean Journal of Parasitology Dec 2022Human infection with simian malaria Plasmodium knowlesi is a cause for concern in Southeast Asian countries, especially in Malaysia. A previous study on Peninsular...
Human infection with simian malaria Plasmodium knowlesi is a cause for concern in Southeast Asian countries, especially in Malaysia. A previous study on Peninsular Malaysia P. knowlesi rhoptry associated protein-1 (PkRAP1) gene has discovered the existence of dimorphism. In this study, genetic analysis of PkRAP1 in a larger number of P. knowlesi samples from Malaysian Borneo was conducted. The PkRAP1 of these P. knowlesi isolates was PCR-amplified and sequenced. The newly obtained PkRAP1 gene sequences (n = 34) were combined with those from the previous study (n = 26) and analysed for polymorphism and natural selection. Sequence analysis revealed a higher genetic diversity of PkRAP1 compared to the previous study. Exon II of the gene had higher diversity (π = 0.0172) than exon I (π = 0.0128). The diversity of the total coding region (π = 0.0167) was much higher than those of RAP1 orthologues such as PfRAP-1 (π = 0.0041) and PvRAP1 (π = 0.00088). Z-test results indicated that the gene was under purifying selection. Phylogenetic tree and haplotype network showed distinct clustering of Peninsular Malaysia and Malaysian Borneo PkRAP1 haplotypes. This geographical-based clustering of PkRAP1 haplotypes provides further evidence of the dimorphism of the gene and possible existence of 2 distinct P. knowlesi lineages in Malaysia.
Topics: Humans; Genetic Variation; Protozoan Proteins; Plasmodium knowlesi; Malaysia; Borneo; Phylogeny; Cluster Analysis
PubMed: 36588415
DOI: 10.3347/kjp.2022.60.6.393 -
Tropical Medicine and Infectious Disease Dec 2022a malaria parasite that occurs naturally in long-tailed macaques, pig-tailed macaques, and banded leaf monkeys, is currently regarded as the fifth of the human malaria...
a malaria parasite that occurs naturally in long-tailed macaques, pig-tailed macaques, and banded leaf monkeys, is currently regarded as the fifth of the human malaria parasites. We aimed to investigate genetic diversity based on the cytochrome oxidase subunit I () gene, detect parasites, and screen for the voltage-gated sodium channel ()-mutation-mediated knockdown resistance () of mosquitoes in Ranong province, which is the most -endemic area in Thailand. One hundred and fourteen females belonging to eight species, including (21.05%), s.s. (20.17%), (19.30%), (19.30%), s.s. (13.16%), A3 (5.26%), (0.88%), and (0.88%), were caught in three geographical regions of Ranong province. None of the mosquitoes sampled in this study were infected with parasites. Based on the sequence analysis of sequences, had the highest level of nucleotide diversity (0.012), followed by (0.011). In contrast, (0.002) had the lowest level of nucleotide diversity. The Fu's and Tajima's values of the species in Ranong were all negative, except the Tajima's values of (0.077). Screening of sequences showed no presence of the mutation of mosquitoes. Our results could be used to further select effective techniques for controlling populations in Thailand's most -endemic area.
PubMed: 36548667
DOI: 10.3390/tropicalmed7120412 -
Frontiers in Cellular and Infection... 2022The spread of artemisinin resistant parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a...
INTRODUCTION
The spread of artemisinin resistant parasites is of global concern and highlights the need to identify new antimalarials for future treatments. Azithromycin, a macrolide antibiotic used clinically against malaria, kills parasites two mechanisms: 'delayed death' by inhibiting the bacterium-like ribosomes of the apicoplast, and 'quick-killing' that kills rapidly across the entire blood stage development.
METHODS
Here, 22 azithromycin analogues were explored for delayed death and quick-killing activities against (the most virulent human malaria) and (a monkey parasite that frequently infects humans).
RESULTS
Seventeen analogues showed improved quick-killing against both species, with up to 38 to 20-fold higher potency over azithromycin after less than 48 or 28 hours of treatment for and , respectively. Quick-killing analogues maintained activity throughout the blood stage lifecycle, including ring stages of parasites (<12 hrs treatment) and were >5-fold more selective against than human cells. Isopentenyl pyrophosphate supplemented parasites that lacked an apicoplast were equally sensitive to quick-killing analogues, confirming that the quick killing activity of these drugs was not directed at the apicoplast. Further, activity against the related apicoplast containing parasite and the gram-positive bacterium did not show improvement over azithromycin, highlighting the specific improvement in antimalarial quick-killing activity. Metabolomic profiling of parasites subjected to the most potent compound showed a build-up of non-haemoglobin derived peptides that was similar to chloroquine, while also exhibiting accumulation of haemoglobin-derived peptides that was absent for chloroquine treatment.
DISCUSSION
The azithromycin analogues characterised in this study expand the structural diversity over previously reported quick-killing compounds and provide new starting points to develop azithromycin analogues with quick-killing antimalarial activity.
Topics: Animals; Humans; Antimalarials; Azithromycin; Parasites; Plasmodium falciparum; Malaria, Falciparum; Chloroquine; Malaria
PubMed: 36530422
DOI: 10.3389/fcimb.2022.1063407 -
The American Journal of Tropical... Jan 2023The five major Plasmodium spp. that cause human malaria appear similar under light microscopy, which raises the possibility that misdiagnosis could routinely occur in... (Meta-Analysis)
Meta-Analysis
The five major Plasmodium spp. that cause human malaria appear similar under light microscopy, which raises the possibility that misdiagnosis could routinely occur in clinical settings. Assessing the extent of misdiagnosis is of particular importance for monitoring P. knowlesi, which cocirculates with the other Plasmodium spp. We performed a systematic review and meta-analysis of studies comparing the performance of microscopy and polymerase chain reaction (PCR) for diagnosing malaria in settings with co-circulation of the five Plasmodium spp. We assessed the extent to which co-circulation of Plasmodium parasites affects diagnostic outcomes. We fit a Bayesian hierarchical latent class model to estimate variation in microscopy sensitivity and specificity measured against PCR as the gold standard. Mean sensitivity of microscopy was low, yet highly variable across Plasmodium spp., ranging from 65.7% (95% confidence interval: 48.1-80.3%) for P. falciparum to 0.525% (95% confidence interval 0.0210-3.11%) for P. ovale. Observed PCR prevalence was positively correlated with estimated microscopic sensitivity and negatively correlated with estimated microscopic specificity, though the strength of the associations varied by species. Our analysis suggests that cocirculation of Plasmodium spp. undermines the accuracy of microscopy. Sensitivity was considerably lower for P. knowlesi, P. malariae, and P. ovale. The negative association between specificity and prevalence imply that less frequently encountered species may be misdiagnosed as more frequently encountered species. Together, these results suggest that the burden of P. knowlesi, P. malariae, and P. ovale may be underappreciated in a clinical setting.
Topics: Humans; Bayes Theorem; Malaria; Malaria, Falciparum; Microscopy; Plasmodium knowlesi; Polymerase Chain Reaction; Communicable Diseases, Emerging; Coinfection; Diagnostic Errors; Plasmodium ovale; Plasmodium malariae
PubMed: 36509046
DOI: 10.4269/ajtmh.21-1155 -
International Journal of Environmental... Nov 2022malaria is a zoonotic infection that affects rural communities in South East Asia. Although the epidemiology of the disease has been extensively researched, the voices...
BACKGROUND
malaria is a zoonotic infection that affects rural communities in South East Asia. Although the epidemiology of the disease has been extensively researched, the voices of individuals within affected communities often go unheard. Here, we describe a study that explores the importance of gatekeepers in conducting research among rural communities, their perspectives on the challenges encountered when attempting to avoid malaria infection, and their views on participatory research.
METHODS
Between 1 November 2021 and 28 February 2022, we conducted a study in Kudat district, Sabah, using a multi-method design. All participants consented to the study, which included health care workers (HCWs) ( = 5), community leaders ( = 8), and faith leaders ( = 1). We conducted interviews, transect walks, and observations with gatekeepers to ensure data trustworthiness. All interviews were conducted in the Sabah Malay dialect. The sessions were audio- and video-recorded, transcribed into English and analyzed using thematic analysis.
RESULTS
Between 2017 and 2021, the number of cases of malaria detected in humans ranged from 35 to 87 in villages under the care of the Lotong primary health care clinic. The challenges in controlling malaria include social norms, lifestyles, socioeconomic factors, environmental factors, and limitations of basic resources. Critical discussions regarding participation with the gatekeepers identified that face-to-face interviews were preferable to online discussions, and influenced willingness to participate in future research.
CONCLUSION
This study was conducted among village gatekeepers during the COVID-19 pandemic and generated information to drive methodological changes, opening up new ideas by sharing perspectives on challenges in malaria control among vulnerable communities. The study generated trust in the community and expanded knowledge regarding participation that is critical for future community-based studies.
Topics: Humans; Plasmodium knowlesi; Rural Population; Community-Based Participatory Research; Pandemics; COVID-19; Malaria; Malaysia
PubMed: 36497837
DOI: 10.3390/ijerph192315764 -
Malaria Journal Dec 2022In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those... (Review)
Review
BACKGROUND
In the last decade Plasmodium knowlesi has been detected in humans throughout South East Asia. The highest risk groups for this infection are males, adults and those performing forest-related work. Furthermore, asymptomatic cases of P. knowlesi malaria have been reported including among women and children.
METHODS
Pubmed, Scopus and the Web of Science databases for literature describing asymptomatic P. knowlesi malaria published between 2010 and 2020 were searched. A systematic literature review was conducted to identify studies reporting the prevalence and incidence of laboratory confirmed asymptomatic P. knowlesi cases in humans, their clinical and demographic characteristics, and methods used to diagnose these cases.
RESULTS
By analysing over 102 papers, thirteen were eligible for this review. Asymptomatic P. knowlesi infections have been detected in 0.03%-4.0% of the population depending on region, and infections have been described in children as young as 2 years old. Various different diagnostic methods were used to detect P. knowlesi cases and there were differing definitions of asymptomatic cases in these studies. The literature indicates that regionally-differing immune-related mechanisms may play a part on the prevalence of asymptomatic P. knowlesi.
CONCLUSION
Differing epidemiological characteristics of asymptomatic P. knowlesi malaria in different regions reinforces the need to further investigate disease transmission mechanics. Effective public health responses to changes in P. knowlesi epidemiology require proactive intervention and multisectoral collaboration.
Topics: Child; Humans; Female; Child, Preschool; Plasmodium knowlesi; Communicable Diseases, Emerging
PubMed: 36474243
DOI: 10.1186/s12936-022-04339-8 -
Parasites & Vectors Dec 2022The production of Plasmodium gametocytes in vitro is a real challenge. Many protocols have been described, but few have resulted in the production of viable and... (Review)
Review
BACKGROUND
The production of Plasmodium gametocytes in vitro is a real challenge. Many protocols have been described, but few have resulted in the production of viable and infectious gametocytes in sufficient quantities to conduct research on-but not limited to-transmission-blocking drug and vaccine development. The aim of this review was to identify and discuss gametocyte production protocols that have been developed over the last two decades.
METHODS
We analyzed the original gametocyte production protocols published from 2000 onwards based on a literature search and a thorough review. A systematic review was performed of relevant articles identified in the PubMed, Web of Sciences and ScienceDirect databases.
RESULTS
A total 23 studies on the production of Plasmodium gametocytes were identified, 19 involving in vitro Plasmodium falciparum, one involving Plasmodium knowlesi and three involving ex vivo Plasmodium vivax. Of the in vitro studies, 90% used environmental stressors to trigger gametocytogenesis. Mature gametocytemia of up to 4% was reported.
CONCLUSIONS
Several biological parameters contribute to an optimal production in vitro of viable and infectious mature gametocytes. The knowledge gained from this systematic review on the molecular mechanisms involved in gametocytogenesis enables reproducible gametocyte protocols with transgenic parasite lines to be set up. This review highlights the need for additional gametocyte production protocols for Plasmodium species other than P. falciparum.
Topics: Humans; Malaria, Falciparum; Plasmodium falciparum; Plasmodium knowlesi; Plasmodium vivax; Systematic Reviews as Topic
PubMed: 36471426
DOI: 10.1186/s13071-022-05566-3 -
BMC Infectious Diseases Dec 2022There are growing reports on the prevalence of non-falciparum species and submicroscopic infections in sub-Saharan African countries but little information is available...
BACKGROUND
There are growing reports on the prevalence of non-falciparum species and submicroscopic infections in sub-Saharan African countries but little information is available from Cameroon.
METHODS
A hospital-based cross-sectional study was carried out in four towns (Douala, Maroua, Mayo-Oulo, and Pette) from three malaria epidemiological strata (Forest, Sahelian, and Soudanian) of Cameroon. Malaria parasites were detected by Giemsa light microscopy and polymerase chain reaction (PCR) assay. Non-falciparum isolates were characterized and their 18S gene sequences were BLASTed for confirmatory diagnosis.
RESULTS
PCR assay detected malaria parasites in 82.4% (98/119) patients, among them 12.2% (12/98) were asymptomatic cases. Three Plasmodium species viz. P. falciparum, P. ovale curtisi and P. vivax, and two co-infection types (P. falciparum + P. vivax and P. falciparum + P. ovale curtisi) were found. The remaining infections were mono-infections with either P. falciparum or P. ovale curtisi. All non-falciparum infections were symptomatic and microscopic. The overall proportion of submicroscopic infections was 11.8% (14/119). Most asymptomatic and submicroscopic infection cases were self-medicated with antimalarial drugs and/or medicinal plants. On analysis, P. ovale curtisi sequences were found to be phylogenetically closer to sequences from India while P. vivax isolates appeared closer to those from Nigeria, India, and Cameroon. No G6PD-d case was found among non-falciparum infections.
CONCLUSIONS
This study confirms our previous work on circulation of P. vivax and P. ovale curtisi and the absence of P. knowlesi in Cameroon. More studies are needed to address non-falciparum malaria along with submicroscopic infections for effective malaria management and control in Cameroon.
Topics: Humans; Cameroon; Cross-Sectional Studies; Malaria; Malaria, Vivax; Antimalarials; Malaria, Falciparum
PubMed: 36460990
DOI: 10.1186/s12879-022-07901-6