-
Nature Communications Aug 2023Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like...
Invasion of red blood cells (RBCs) by Plasmodium merozoites is critical to their continued survival within the host. Two major protein families, the Duffy binding-like proteins (DBPs/EBAs) and the reticulocyte binding like proteins (RBLs/RHs) have been studied extensively in P. falciparum and are hypothesized to have overlapping, but critical roles just prior to host cell entry. The zoonotic malaria parasite, P. knowlesi, has larger invasive merozoites and contains a smaller, less redundant, DBP and RBL repertoire than P. falciparum. One DBP (DBPα) and one RBL, normocyte binding protein Xa (NBPXa) are essential for invasion of human RBCs. Taking advantage of the unique biological features of P. knowlesi and iterative CRISPR-Cas9 genome editing, we determine the precise order of key invasion milestones and demonstrate distinct roles for each family. These distinct roles support a mechanism for phased commitment to invasion and can be targeted synergistically with invasion inhibitory antibodies.
Topics: Animals; Humans; Carrier Proteins; Parasites; Malaria; Plasmodium knowlesi; Protozoan Proteins; Erythrocytes; Merozoites; Plasmodium falciparum
PubMed: 37528099
DOI: 10.1038/s41467-023-40357-z -
Genes Jun 2023Although Malaysia is considered free of human malaria, there has been a growing number of cases. This alarming trend highlighted the need for our understanding of this...
Although Malaysia is considered free of human malaria, there has been a growing number of cases. This alarming trend highlighted the need for our understanding of this parasite and its associated vectors, especially considering the role of genetic diversity in the adaptation and evolution among vectors in endemic areas, which is currently a significant knowledge gap in their fundamental biology. Thus, this study aimed to investigate the genetic diversity of , , , and -the vectors for malaria in Malaysia. Based on cytochrome c oxidase 1 () and internal transcribed spacer 2 () markers, the genealogic networks of showed a separation of the haplotypes between Peninsular Malaysia and Malaysia Borneo, forming two distinct clusters. Additionally, the genetic distances between these clusters were high (2.3-5.2% for ) and (2.3-4.7% for ), indicating the likely presence of two distinct species or cryptic species within . In contrast, no distinct clusters were observed in , , or , implying a lack of pronounced genetic differentiation among their populations. It is worth noting that there were varying levels of polymorphism observed across the different subpopulations, highlighting some levels of genetic variation within these mosquito species. Nevertheless, further analyses revealed that all four species have undergone demographic expansion, suggesting population growth and potential range expansion for these vectors in this region.
Topics: Humans; Animals; Malaria; Anopheles; Plasmodium knowlesi; Malaysia; Mosquito Vectors; Demography
PubMed: 37510274
DOI: 10.3390/genes14071369 -
Mikrobiyoloji Bulteni Jul 2023Malaria is a serious, contagious infection caused by single-celled parasites. About 200 species of Plasmodium have been described that can cause infection in...
Malaria is a serious, contagious infection caused by single-celled parasites. About 200 species of Plasmodium have been described that can cause infection in vertebrates. Five different species of Plasmodium are known to cause infection in humans to date. Infection with more than one type of pathogen is called coinfection. This type of infections can be caused by different species of the same genus, as well as by different species. Malaria coinfections are mostly caused by the combination of Plasmodium vivax and Plasmodium falciparum. In this study, a case of malaria admitted to the hospital and diagnosed was presented. Thin smear blood preparations were prepared from the peripheral blood of a 54 year-old Republic of Türkiye citizen male patient who applied to the emergency department with fever and chills. The preparations were stained with Giemsa and examined under a microscope with a x 100 objective, and trophozoite and gametocyte forms belonging to Plasmodium genus were determined. As a result of probe-based quantitative real-time polymerase chain reaction (qRt-PCR) study with primers specific to Plasmodium vivax, Plasmodium malariae, Plasmodium falciparum, Plasmodium ovale and Plasmodium knowlesi for definitive species identification, co-infection of P.vivax, P.falciparum, P.ovale and P.knowlesi was detected in the patient. In addition, it was proved that our patient was infected with four different species by conventional PCR study in which five species were studied and then by DNA sequence analysis. On the fourth day of artemether-lumefantrine treatment, the patient's fever response was observed and the trophozoite forms disappeared from the third day in the daily peripheral smear follow-up. Since P.vivax and P.ovale species were also detected after species determination by molecular methods, primaquine 1 x 30 mg tablet was added to the existing drugs for the treatment of hypnozoite forms of the parasite. In recent years, there has been an increase in malaria imported cases, especially after visits to African countries. Such rare cases of malaria coinfection may be encountered during visits to geographies located at the intersection of endemic regions. According to the data of the World Health Organization, maximum attention should be paid to the prevention and prophylaxis protocols from vectors, especially in travels to countries with the highest mortality and morbidity. In co-infection cases similar to our patient, for tertian malaria and tertiary ovale malaria, hypnozoid therapy should not be overlooked. When the insecticide-resistant vectors and drug-resistant Plasmodium strains encountered in recent years are evaluated as a whole, there is a need to develop more effective strategies in the fight against malaria. In addition to microscopic examination, which is accepted as the gold standard, we believe that evaluating molecular studies together in diagnosis is extremely important for the treatment process when hypnozoite periods are considered.
Topics: Animals; Male; Humans; Middle Aged; Coinfection; Antimalarials; Cameroon; Artemether; Artemether, Lumefantrine Drug Combination; Malaria; Malaria, Vivax; Plasmodium; Plasmodium falciparum; Plasmodium vivax; Real-Time Polymerase Chain Reaction
PubMed: 37462313
DOI: 10.5578/mb.20239942 -
Scientific Reports Jul 2023Molecular detection methods have revealed higher sensitivity and specificity than conventional microscopy or rapid diagnostic tests for malaria diagnosis. In this study,...
Molecular detection methods have revealed higher sensitivity and specificity than conventional microscopy or rapid diagnostic tests for malaria diagnosis. In this study, we implemented, evaluated and validated according to the ISO 15,189 requirements, a multiplex real-time PCR assay to detect and identify the five human malaria parasites. DNA samples were extracted from whole blood or dried blood spots drawn from patients. Based on the External Quality Assessment (whole blood), this method shows 100% sensitivity and specificity. This PCR detected P. vivax up to 0.25 p/µl, P. falciparum and P. knowlesi up to 0.5 p/µl, P. ovale up to 1 p/µl and P. malariae up to 5 p/µl of blood. From blood spots (extraction from four punches), it detected P. vivax at 5 p/µl, P. falciparum, P. ovale and P. knowlesi at 20 p/µl and P. malariae at 125 p/µl. In conclusion, this quantitative PCR shows excellent performance, is easy to use and DNA saver. It is especially useful to actively screen large population groups and identify the five human malaria parasites in a context of low malaria transmission.
Topics: Humans; Real-Time Polymerase Chain Reaction; Plasmodium; Malaria; Malaria, Vivax; Malaria, Falciparum; Sensitivity and Specificity; Plasmodium vivax; Plasmodium falciparum
PubMed: 37452123
DOI: 10.1038/s41598-023-38621-9 -
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 -
PLoS Neglected Tropical Diseases Jun 2023The elimination of malaria in Southeast Asia has become more challenging as a result of rising knowlesi malaria cases. In addition, naturally occurring human infections...
BACKGROUND
The elimination of malaria in Southeast Asia has become more challenging as a result of rising knowlesi malaria cases. In addition, naturally occurring human infections with other zoonotic simian malaria caused by Plasmodium cynomolgi and Plasmodium inui adds another level of complexity in malaria elimination in this region. Unfortunately, data on vectors which are responsible for transmitting this zoonotic disease is very limited.
METHODOLOGY/PRINCIPAL FINDINGS
We conducted longitudinal studies to investigate the entomological parameters of the simian malaria vectors and to examine the genetic diversity and evolutionary pattern of their simian Plasmodium. All the captured Anopheles mosquitoes were dissected to examine for the presence of oocysts, sporozoites and to determine the parous rate. Our study revealed that the Anopheles Leucosphyrus Group mosquitoes are highly potential competent vectors, as evidenced by their high rate of parity, survival and sporozoite infections in these mosquitoes. Thus, these mosquitoes represent a risk of human infection with zoonotic simian malaria in this region. Haplotype analysis on P. cynomolgi and P. inui, found in high prevalence in the Anopheles mosquitoes from this study, had shown close relationship between simian Plasmodium from the Anopheles mosquitoes with its vertebrate hosts. This directly signifies the ongoing transmission between the vector, macaques, and humans. Furthermore, population genetic analysis showed significant negative values which suggest that both Plasmodium species are undergoing population expansion.
CONCLUSIONS/SIGNIFICANCE
With constant microevolutionary processes, there are potential for both P. inui and P. cynomolgi to emerge and spread as a major public health problem, following the similar trend of P. knowlesi. Therefore, concerted vector studies in other parts of Southeast Asia are warranted to better comprehend the transmission dynamics of this zoonotic simian malaria which eventually would aid in the implementation of effective control measures in a rapidly changing environment.
Topics: Animals; Humans; Malaria; Plasmodium cynomolgi; Anopheles; Parasites; Mosquito Vectors; Plasmodium; Macaca; Plasmodium knowlesi
PubMed: 37384790
DOI: 10.1371/journal.pntd.0011438 -
The American Journal of Tropical... Aug 2023Severe malaria after splenectomy has been reported with infections with Plasmodium falciparum, Plasmodium knowlesi, and Plasmodium malariae, but is less...
Severe malaria after splenectomy has been reported with infections with Plasmodium falciparum, Plasmodium knowlesi, and Plasmodium malariae, but is less well-characterized with Plasmodium vivax. We describe a case of severe P. vivax malaria with hypotension, prostration, and acute kidney injury occurring 2 months after splenectomy in Papua, Indonesia. The patient was treated successfully with intravenous artesunate.
Topics: Humans; Malaria, Vivax; Splenectomy; Malaria; Artesunate; Plasmodium vivax; Plasmodium falciparum
PubMed: 37339765
DOI: 10.4269/ajtmh.23-0147 -
Scientific Reports Jun 2023To date, four species of simian malaria parasites including Plasmodium knowlesi, P. cynomolgi, P. inui and P. fieldi have been incriminated in human infections in...
To date, four species of simian malaria parasites including Plasmodium knowlesi, P. cynomolgi, P. inui and P. fieldi have been incriminated in human infections in Thailand. Although the prevalence of malaria in macaque natural hosts has been investigated, their vectors remain unknown in this country. Herein, we performed a survey of Anopheles mosquitoes during rainy and dry seasons in Narathiwat Province, Southern Thailand. Altogether 367 Anopheles mosquitoes were captured for 40 nights during 18:00 to 06:00 h by using human-landing catches. Based on morphological and molecular identification, species composition comprised An. maculatus (37.06%), An. barbirostris s.l. (31.34%), An. latens (17.71%), An. introlatus (10.08%) and others (3.81%) including An. umbrosus s.l., An. minimus, An. hyrcanus s.l., An. aconitus, An. macarthuri and An. kochi. Analyses of individual mosquitoes by PCR, sequencing and phylogenetic inference of the mitochondrial cytochrome genes of both malaria parasites and mosquitoes have revealed that the salivary gland samples of An. latens harbored P. knowlesi (n = 1), P. inui (n = 2), P. fieldi (n = 1), P. coatneyi (n = 1), P. hylobati (n = 1) and an unnamed Plasmodium species known to infect both long-tailed and pig-tailed macaques (n = 2). The salivary glands of An. introlatus possessed P. cynomolgi (n = 1), P. inui (n = 1), P. hylobati (n = 1) and coexistence of P. knowlesi and P. inui (n = 1). An avian malaria parasite P. juxtanucleare has been identified in the salivary gland sample of An. latens. Three other distinct lineages of Plasmodium with phylogenetic affinity to avian malaria species were detected in An. latens, An. introlatus and An. macarthuri. Interestingly, the salivary gland sample of An. maculatus contained P. caprae, an ungulate malaria parasite known to infect domestic goats. Most infected mosquitoes harbored multiclonal Plasmodium infections. All Plasmodium-infected mosquitoes were captured during the first quarter of the night and predominantly occurred during rainy season. Since simian malaria in humans has a wide geographic distribution in Thailand, further studies in other endemic areas of the country are mandatory for understanding transmission and prevention of zoonotic malaria.
Topics: Animals; Humans; Plasmodium knowlesi; Parasites; Phylogeny; Thailand; Malaria, Avian; Mosquito Vectors; Plasmodium; Malaria; Primates; Macaca; Anopheles
PubMed: 37264067
DOI: 10.1038/s41598-023-36017-3