Plasmodium—a brief introduction to the parasites causing human malaria and their basic biology

Malaria is one of the most devastating infectious diseases of humans. It is problematic clinically and economically as it prevails in poorer countries and regions, strongly hindering socioeconomic development. The causative agents of malaria are unicellular protozoan parasites belonging to the genus Plasmodium. These parasites infect not only humans but also other vertebrates, from reptiles and birds to mammals. To date, over 200 species of Plasmodium have been formally described, and each species infects a certain range of hosts. Plasmodium species that naturally infect humans and cause malaria in large areas of the world are limited to five—P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi. The first four are specific for humans, while P. knowlesi is naturally maintained in macaque monkeys and causes zoonotic malaria widely in South East Asia. Transmission of Plasmodium species between vertebrate hosts depends on an insect vector, which is usually the mosquito. The vector is not just a carrier but the definitive host, where sexual reproduction of Plasmodium species occurs, and the parasite’s development in the insect is essential for transmission to the next vertebrate host. The range of insect species that can support the critical development of Plasmodium depends on the individual parasite species, but all five Plasmodium species causing malaria in humans are transmitted exclusively by anopheline mosquitoes. Plasmodium species have remarkable genetic flexibility which lets them adapt to alterations in the environment, giving them the potential to quickly develop resistance to therapeutics such as antimalarials and to change host specificity. In this article, selected topics involving the Plasmodium species that cause malaria in humans are reviewed. © 2021, The Author(s)

Correction to: Plasmodium—a brief introduction to the parasites causing human malaria and their basic biology

Malaria is one of the most devastating infectious diseases of humans. It is problematic clinically and economically as it prevails in poorer countries and regions, strongly hindering socioeconomic development. The causative agents of malaria are unicellular protozoan parasites belonging to the genus Plasmodium. These parasites infect not only humans but also other vertebrates, from reptiles and birds to mammals. To date, over 200 species of Plasmodium have been formally described, and each species infects a certain range of hosts. Plasmodium species that naturally infect humans and cause malaria in large areas of the world are limited to five—P. falciparum, P. vivax, P. malariae, P. ovale and P. knowlesi. The first four are specific for humans, while P. knowlesi is naturally maintained in macaque monkeys and causes zoonotic malaria widely in South East Asia. Transmission of Plasmodium species between vertebrate hosts depends on an insect vector, which is usually the mosquito. The vector is not just a carrier but the definitive host, where sexual reproduction of Plasmodium species occurs, and the parasite’s development in the insect is essential for transmission to the next vertebrate host. The range of insect species that can support the critical development of Plasmodium depends on the individual parasite species, but all five Plasmodium species causing malaria in humans are transmitted exclusively by anopheline mosquitoes. Plasmodium species have remarkable genetic flexibility which lets them adapt to alterations in the environment, giving them the potential to quickly develop resistance to therapeutics such as antimalarials and to change host specificity. In this article, selected topics involving the Plasmodium species that cause malaria in humans are reviewed

Method for the separation of mitochondria and apicoplast from the malaria parasite Plasmodium falciparum

The growth and the survival of the human malaria parasite Plasmodium falciparum are critically dependent on the functions of the two organelles - the mitochondrion and the apicoplast. However, these two organelles have been known to be difficult to separate from each other when they are released from Plasmodium cell. We have been searching for the conditions with which separation of the mitochondrion and the apicoplast is achieved. In this study, we investigated how the two organelle's separation is affected when the pressure of the nitrogen gas to disrupt the Plasmodium cells by nitrogen cavitation method is lowered from the pressure regularly applied (1200 psi). The parasite cell was sufficiently disrupted even when nitrogen cavitation was carried out at 300 psi. The obtained mitochondrial sample was much less contaminated by DNA compared with the sample prepared using the gas at the regular pressure. After the fractionation by Percoll density gradient, the mitochondrion and the apicoplast from the 300 psi cell lysate exhibited different separation profiles. This is the first experimental evidence that indicates the mitochondrion and the apicoplast of P. falciparumare separable from each other

契約破棄と両側の法的救済

本稿では不完備契約モデルにおいて,どのような法的救済制度が望ましく,また,いかなる契約が有利であるのかを分析し

Recent Incidence of Human Malaria Caused by Plasmodium knowlesi in the Villages in Kudat Peninsula, Sabah, Malaysia: Mapping of The Infection Risk Using Remote Sensing Data

Plasmodium knowlesi (Pk) is a malaria parasite that naturally infects macaque monkeys in Southeast Asia. Pk malaria, the zoonosis transmitted from the infected monkeys to the humans by Anopheles mosquito vectors, is now a serious health problem in Malaysian Borneo. To createa strategic plan to control Pk malaria, it is important to estimate the occurrence of the disease correctly. The rise of Pk malaria has been explained as being due to ecological changes, especially deforestation. In this research, we analysed the time-series satellite images of MODIS (MODerate-resolution Imaging Spectroradiometer) of the Kudat Peninsula in Sabah and created the “Pk risk map” on which the Land-Use and Land-Cover (LULC) information was visualised. The case number of Pk malaria of a village appeared to have a correlation with the quantity of two specific LULC classes, the mosaic landscape of oil palm groves and the nearby land-use patches of dense forest, surrounding the village. Applying a Poisson multivariate regression with a generalized linear mixture model (GLMM), the occurrence of Pk malaria cases was estimated from the population and the quantified LULC distribution on the map. The obtained estimations explained the real case numbers well, when the contribution of another risk factor, possibly the occupation of the villagers, is considered. This implies that the occurrence of the Pk malaria cases of a village can be predictable from the population of the village and the LULC distribution shown around it on the map. The Pk risk map will help to assess the Pk malaria risk distributions quantitatively and to discover the hidden key factors behind the spread of this zoonosis

通塾が中学生の就寝時間や疲労感に与える影響に関する研究

To investigate the influence of attending juku on bedtime and cumulative fatigue symptoms, questionnaires were administered to 163 students in a junior high school in Aichi Prefecture. Cumulative fatigue were assessed by using the Cumulative Fatigue Symptoms Index (CFSI). The results were as follows : 1) Approximately 70 percent of students attended some kind of juku, 40 percent of which changed bedtime when attending juku. No tendency was found between the change in supper time and the change in bedtime. 2) As a result, in the group whose bedtime got late when attending juku, the average rates of those who complained of symptoms within chronic tiredness rose. On the other hand, in the group without attending juku the average rates of those who complained of symptoms within physical disorders, decreased vitality, decreased willingness to study, irritability were higher than those in the group attending juku. 3) The complaint rates of load and tiredness were high in the group who usually goes to bed after 0 a. m.. 4) Average rates of those who complained of symptoms within many categories were high in the group without attending juku and usually going to bed from 11 p. m. to 0 a. m. On the other hand, average rates of those who complained of symptoms within irritability were a little high in the group who usually goes to bed from 11 p. m. to 0 a. m. and got late bedtime with attending juku

Serum IgG4 as a biomarker reflecting pathophysiology and post-operative recurrence in chronic rhinosinusitis

Background: Type 2 chronic rhinosinusitis (CRS), especially eosinophilic CRS (ECRS), is an intractable upper airway inflammatory disease. Establishment of serum biomarkers reflecting the pathophysiology of CRS is desirable in a clinical setting. As IgG4 production is regulated by type 2 cytokines, we sought to determine whether serum IgG4 levels can be used as a biomarker for CRS. Methods: Association between the serum IgG4 levels and clinicopathological factors was analyzed in 336 CRS patients. Receiver operating characteristics (ROC) analysis was performed to determine the cut-off value of serum IgG4 levels that can be used to predict the post-operative recurrence. Results: Serum IgG4 levels were significantly higher in patients with moderate to severe ECRS versus those with non to mild ECRS. The levels were also significantly higher in asthmatic patients and patients exhibiting recurrence after surgery compared to controls. ROC analysis determined that the best cut-off value for the serum IgG4 level to predict the post-operative recurrence was 95 mg/dL. The corresponding sensitivity and specificity were 39.7% and 80.5%, respectively. When we combined the two cut-off values for the serum IgG4 and periostin, patients with high serum levels of either IgG4 or periostin exhibited a high post-operative recurrence (OR: 3.95) as compared to patients having low serum levels of both IgG4 and periostin. Conclusions: The present results demonstrate that the serum IgG4 level is associated with disease severity and post-operative course in CRS. In particular, the combination of serum IgG4 and periostin could be a novel biomarker that predicts post-operative recurrence

Structural and Biochemical Features of Eimeria tenella Dihydroorotate Dehydrogenase, a Potential Drug Target

Dihydroorotate dehydrogenase (DHODH) is a mitochondrial monotopic membrane protein that plays an essential role in the pyrimidine de novo biosynthesis and electron transport chain pathways. In Eimeria tenella, an intracellular apicomplexan parasite that causes the most severe form of chicken coccidiosis, the activity of pyrimidine salvage pathway at the intracellular stage is negligible and it relies on the pyrimidine de novo biosynthesis pathway. Therefore, the enzymes of the de novo pathway are considered potential drug target candidates for the design of compounds with activity against this parasite. Although, DHODHs from E. tenella (EtDHODH), Plasmodium falciparum (PfDHODH), and human (HsDHODH) show distinct sensitivities to classical DHODH inhibitors, in this paper,we identify ferulenol as a potent inhibitor of both EtDHODH and HsDHODH. Additionally, we report the crystal structures of EtDHODH and HsDHODH in the absence and presence of ferulenol. Comparison of these enzymes showed that despite similar overall structures, the EtDHODH has a long insertion in the N-terminal helix region that assumes a disordered configuration. In addition, the crystal structures revealed that the ferulenol binding pocket of EtDHODH is larger than that of HsDHODH. These differences can be explored to accelerate structure-based design of inhibitors specifically targeting EtDHODH