Molecular basis of fosmidomycin's action on the human malaria parasite Plasmodium falciparum
99
Citation
41
Reference
10
Related Paper
Citation Trend
Abstract:
The human malaria parasite Plasmodium falciparum is responsible for the deaths of more than a million people each year. Fosmidomycin has been proven to be efficient in the treatment of P. falciparum malaria by inhibiting 1-deoxy-D-xylulose 5-phosphate reductoisomerase (DXR), an enzyme of the non-mevalonate pathway, which is absent in humans. However, the structural details of DXR inhibition by fosmidomycin in P. falciparum are unknown. Here, we report the crystal structures of fosmidomycin-bound complete quaternary complexes of PfDXR. Our study revealed that (i) an intrinsic flexibility of the PfDXR molecule accounts for an induced-fit movement to accommodate the bound inhibitor in the active site and (ii) a cis arrangement of the oxygen atoms of the hydroxamate group of the bound inhibitor is essential for tight binding of the inhibitor to the active site metal. We expect the present structures to be useful guides for the design of more effective antimalarial compounds.Intraleucocytic malaria pigment has been suggested as a measure of disease severity in malaria. We have tested this hypothesis by studying 146 children aged 6 months to 14 years in 4 categories--cerebral malaria, mild malaria, asymptomatic malaria and 'no malaria'--in Ibadan, Nigeria, an area of intense malaria transmission in Africa. Children with cerebral malaria were studied at the university hospital, those with mild malaria at 2 primary health centres and the other 2 groups were studied in a primary school. The proportion of pigment-containing neutrophils showed a clear rise across the spectrum no malaria--asymptomatic malaria--mild malaria--cerebral malaria (median values 2.0%, 6.5%, 9.0% and 27.0%, respectively; P < 0.0001). The proportion of pigment-containing monocytes did not differ significantly between the mild malaria, asymptomatic malaria and no malaria groups but the cerebral malaria group had a higher median value than the other 3 groups. The ratio of pigment-containing neutrophils to pigment-containing monocytes showed the same trend across the groups of subjects as was observed with the number of pigment-containing neutrophils. It is concluded that the pigment-containing neutrophil count is a simple marker of disease severity in childhood malaria in addition to the parasite count.
Cerebral Malaria
Cite
Citations (109)
Objective To study the malaria epidemic characteristics and control measures, so as to control malaria and eradicate falciparum malaria in Guangxi Autonomous Region of China. Methods During attack phase integrated measures were taken to control falciparum malaria in natural villages which were classified according to the prevalence of malaria; post control of malaria, the major control measure was seeking and getting rid of the malaria infection source through examining the fever patients and the annul blood examination rate was up to 10%. Results The malaria morbidity in Guangxi was reduced from 296.7 to 0.07; during 1997-2001 a total of 6 241 011 fever patients and foci residents were examined and only 485 cases of vivax malaria were found out, but falciparum malaria was not discovered. Conclusion The measures were very effective for basically eliminating malaria and falciparum malaria in Guangxi.
Vivax malaria
Cite
Citations (0)
[Objective]To understand the malaria prevalence before and after basic elimination of malaria in the county.[Methods]Collected and collated the internal and external sources of malaria in the county from 1980-2008.Excel statistical software was used for statistical analysis.[Results]During the last 28 years,there 1 128 malaria cases were reported.Before eradication of malaria,48.32% were the local malaria patients,51.68% were the floating population.After the malaria eradication,it found all 116 malaria cases were floating population.The places where the population infected were respectively 65.25% for Hainan,10.80% for Guangdong,2.66% Myanma,2.19% Yunnan.And Plasmodium falciparum malaria and mixed infection were found.[Conclusion]After the eradication of malaria,internal malaria patients are not found in the county.Malaria cases are mainly from the floating population.It dose not find secondary malaria patients.The effect of anti-malaria has been consolidated.
Floating population
Cite
Citations (0)
A small molecule can cure malaria infections in mice with a single dose, researchers report. They also show that the malaria parasite Plasmodium falciparum has a tough time developing resistance to the compound, known as MMV688533. If shown to be safe and effective in people, MMV688533 could be a powerful weapon in the fight against malaria. Malaria infections and deaths declined between 2000 and 2015 thanks to preventative measures, diagnostics, and therapeutics, but the number of people who get malaria has plateaued since 2016. Malaria parasites in Southeast Asia have developed resistance to the current arsenal of antimalarial drugs, making them ineffective in many cases. This same resistance threatens to become a problem in Africa, where malaria takes the biggest toll. Malaria killed about 409,000 people in 2019, according to the World Health Organization. "It could easily get a lot worse if we lose our first-line drugs," says malaria researcher
Death toll
Plasmodium (life cycle)
Malarial parasites
Cite
Citations (0)
More than 200 million people worldwide contract malaria from mosquito bites. In sub-Saharan Africa, 100 million clinical cases of malaria are reported every year, resulting in almost one million deaths. Malaria has been implicated in the causation of deafness in several studies in the West Africa subregion. This paper examines the association between malaria and deafness, and considers which factors may be involved in the causation of deafness. Although age, immunity, the type of malaria parasite, fever, complications of malaria, and complications resulting from the drug treatment of malaria may contribute to the development of deafness in malaria, the actual mechanism of causation is not clearly understood. Deafness in malaria is associated with P. falciparum parasitic infection. The author is certain that the high fever in malaria, leading to febrile convulsions and cerebral involvement, can result in deafness. Further investigation is needed to determine whether the presence of untreated malaria parasites in the blood causes deafness.
Cerebral Malaria
Causation
Cite
Citations (10)
After mentioning the main differences between malaria control and malaria eradication, it is suggested that all anti–malaria activities in Iran should be renamed as malaria control. Applied research in malaria is identified into four categories covering the following subjects. 1- Malaria parasites and anti-malaria drugs. 2- Malaria vectors. 3- Malaria in the community. 4- Use of epidemiological techniques in malaria field research. Various research programs that at present could or should be carried out in each category have been discussed in the text.
Cite
Citations (0)
Plasmodium infection causes devastating disease and high mortality in young children. Immunity develops progressively as children acquire protection against severe disease, although reinfections and recrudescences still occur throughout life in areas of endemicity, partly due to parasite immunoevasion via switching of variant proteins such as Plasmodium falciparum erythrocyte membrane protein 1 (PfEMP1) expressed on the infected erythrocyte surface.
Plasmodium (life cycle)
Cite
Citations (3)
Active compound
Cite
Citations (5)
Objective To undersand the results of malaria control in Hainan a year after simplementation of Global Fund Malaria Projexct and provide evidence for elimination of malaria in Hainan province.Methods Data of malaria project activities in Hainan from July,2010 to July,2011 were collected and analyzed.Results No Plasmodium falciparum malaria cases were reported from 2010 to 2011,annual blood microscopy rate was 1.39%;the standard treatment rate of malaria cases was 90%.Conclusion The microscopy examiantion rate and standard treatment rate of of malaria infections attained the requirements of Glopbal Fund Malaria Project.
Cite
Citations (0)
Malaria may be encountered in parts of South Africa not known to have malaria, in ways not typical of how it is usually transmitted or acquired. In this issue of SAMJ two articles discuss two clinical forms of malaria in non-endemic areas, imported malaria and odyssean malaria. Imported malaria is defined as malaria presenting in a country other than that in which it was acquired, while odyssean malaria is acquired in non-malarious area from the bite of an imported mosquito. Imported and odyssean malaria are important because of the high incidence of complications and mortality often associated with them, and should be remembered as a cause of unexplained fever and thrombocytopenia. Key to reducing the complications and mortality related to malaria is early recognition and treatment.
Cite
Citations (3)