Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024530 (malaria)
 44,886 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The macaque malaria parasite Plasmodium knowlesi has recently emerged as an important zoonosis in Southeast Asia. Infections are typically mild but can cause severe disease, achieving parasite densities similar to fatal Plasmodium falciparum infections. Here we show that a primate-adapted P. knowlesi parasite proliferates poorly in human blood due to a strong preference for young red blood cells (RBCs). We establish a continuous in vitro culture system by using human blood enriched for young cells. Mathematical modelling predicts that parasite adaptation for invasion of older RBCs is a likely mechanism leading to high parasite densities in clinical infections. Consistent with this model, we find that P. knowlesi can adapt to invade a wider age range of RBCs, resulting in proliferation in normal human blood. Such cellular niche expansion may increase pathogenesis in humans and will be a key feature to monitor as P. knowlesi emerges in human populations.
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PMID:Expansion of host cellular niche can drive adaptation of a zoonotic malaria parasite to humans. 2353 59

Infections caused by protozoan parasites are among the most widespread and intractable transmissible diseases affecting the developing world, with malaria and leishmaniasis being the most costly in terms of morbidity and mortality. Although new drugs are urgently required against both diseases in the face of ever-rising resistance to frontline therapies, very few candidates passing through development pipelines possess a known and novel mode of action. Set in the context of drugs currently in use and under development, we present the evidence for N-myristoyltransferase (NMT), an enzyme that N-terminally lipidates a wide range of specific target proteins through post-translational modification, as a potential drug target in malaria and the leishmaniases. We discuss the limitations of current knowledge regarding the downstream targets of this enzyme in protozoa, and our recent progress towards potent cell-active NMT inhibitors against the most clinically-relevant species of parasite. Finally, we outline the next steps required in terms of both tools to understand N-myristoylation in protozoan parasites, and the generation of potential development candidates based on the output of our recently-reported high-throughput screens.
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PMID:N-Myristoyltransferase as a potential drug target in malaria and leishmaniasis. 2361 Nov 9

Malaria has never been endemic in New Zealand, and all cases have been diagnosed in international travelers. In this paper, we describe malaria cases reported from 1997 to 2009 and discuss epidemiological changes compared to a previous report from 1980 to 1992. From 1997 to 2009, 666 malaria infections were reported, with 410 cases (61.6%) in travelers aged 20-39 and 133 (20%) in military personnel. Infections were caused by Plasmodium vivax in 436 cases (72.7%) and Plasmodium falciparum in 163 (27.2%). In the 533 civilians, common countries of infection were Papua New Guinea (24.4%), India (18.6%), the Solomon Islands (8.8%), and Indonesia (6.1%). Most common regions of malaria acquisition for civilians were Papua New Guinea and Western Pacific (39.8%), Africa (24.7%), Indian subcontinent (19.5%), and Southeast Asia (13.6%). Compared to a previous report of malaria in New Zealand from 1980 to 1992, regions of malaria acquisition have changed significantly, with a lower percentage of cases acquired from Papua New Guinea and Western Pacific (from 59.2% to 39.3%), and a higher percentage from Africa (from 8.6% to 21.3%). The ethnic groups affected also differ significantly between the two surveillance periods, with a reduction in the percentage of cases reported in Caucasians (from 80.8 to 45.9%) and an increase in cases in Indians (from 7.0 to 15.7%), Papua New Guineans and Pacific Islanders (from 5.2 to 16.9%), other Asians (from 2.3 to 5.6%), and Africans (from 0 to 8.5%). Common locations of malaria infection have evolved over time and probably reflect changing travel patterns of New Zealanders and the origins of visitors and immigrants. Therefore, local surveillance is important for informing pretravel advice by identifying vulnerable groups and common destinations for malaria infection, so that special attention on malaria prevention can be focused on travelers who are at highest risk. Ongoing surveillance is also essential for monitoring the evolving epidemiology of imported malaria over time.
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PMID:The importance of surveillance for informing pretravel medical advice: imported malaria in New Zealand 1997-2009. 2445 29

Infections with the malaria parasite Plasmodium vivax are noteworthy for potentially very long incubation periods (6-9 months), which present a major barrier to disease elimination. Increased sporozoite challenge has been reported to be associated with both shorter incubation and pre-patent periods in a range of human challenge studies. However, this evidence base has scant empirical foundation, as these historical analyses were limited by available analytic methods, and provides no quantitative estimates of effect size. Following a comprehensive literature search, we re-analysed all identified studies using survival and/or logistic models plus contingency tables. We have found very weak evidence for dose-dependence at entomologically plausible inocula levels. These results strongly suggest that sporozoite dosage is not an important driver of long-latency. Evidence presented suggests that parasite strain and vector species have quantitatively greater impacts, and the potential existence of a dose threshold for human dose-response to sporozoites. Greater consideration of the complex interplay between these aspects of vectors and parasites are important for human challenge experiments, vaccine trials, and epidemiology towards global malaria elimination.
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PMID:Re-assessing the relationship between sporozoite dose and incubation period in Plasmodium vivax malaria: a systematic re-analysis. 2452 62

Antimicrobial drug resistance is usually not monitored in under-resourced countries because they lack surveillance networks, laboratory capacity, and appropriate diagnostics. This accelerating problem accounts for substantial number of excess deaths, especially among infants. Infections particularly affected by antimicrobial drug resistance include tuberculosis, malaria, severe acute respiratory infections, and sepsis caused by gram-negative bacteria. Nonetheless, mapping antimicrobial drug resistance is feasible in under-resourced countries, and lessons can be learned from previous successful efforts. Specimen shipping conditions, data standardization, absence of contamination, and adequate diagnostics must be ensured. As a first step toward solving this problem, we propose that a road map be created at the international level to strengthen antimicrobial resistance surveillance in under-resourced countries. This effort should include a research agenda; a map of existing networks and recommendations to unite them; and a communication plan for national, regional, and international organizations and funding agencies.
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PMID:Surveillance for antimicrobial drug resistance in under-resourced countries. 2456 6

Plasmodium knowlesi is the fifth species of Plasmodium recently identified to cause human malaria. Infections with P. knowlesi are currently being reported from South-East Asian countries and the incidence is on the rise with a possibility of spread to the geographically contiguous countries. P. knowlesi infections can result in a high degree of parasitemia causing severe malaria in a larger proportion of infected individuals. If detected early and treated with appropriate antimicrobials, these infections show a significant clinical improvement. The widely used microscopic methods usually misidentify P. knowlesi as the less pathogenic Plasmodium malariae leading to inadequate therapy and adverse clinical outcomes. The currently popular rapid immuno-chromatographic card tests have a very low sensitivity in diagnosing knowlesi malaria and can erroneously report P. knowlesi as other Plasmodia and vice-versa. At present molecular methods are the most efficacious in diagnosing P. knowlesi infections, but these tests can produce a false positive report in Plasmodium vivax infections and require expensive equipment and trained personnel. An ideal diagnostic test for P. knowlesi infections, which is potent, cost-effective and practically feasible in the resource limited setting is yet to be developed.
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PMID:Challenges in diagnosis of Plasmodium knowlesi infections. 2475 23

Pregnant women become susceptible to malaria infection despite their acquired immunity to this disease from childhood. The placental sequestration of Plasmodium falciparum infected erythrocytes (IE) is the major feature of malaria during pregnancy, due to ability of these parasites to bind chondroitin sulfate A (CSA) in the placenta through the VAR2CSA protein that parasites express on the surface of IE. We collected parasites at different times of pregnancy and investigated the adhesion pattern of freshly collected isolates on the three well described host receptors (CSPG, CD36 and ICAM-1). Var genes transcription profile and VAR2CSA surface-expression were assessed in these isolates. Although adhesion of IE to CD36 and ICAM-1 was observed in some isolates, CSA-adhesion was the predominant binding feature in all isolates analyzed. Co-existence in the peripheral blood of several adhesion phenotypes in early pregnancy isolates was observed, a diversity that gradually tightens with gestational age in favour of the CSA-adhesion phenotype. Infections occurring in primigravidae were often by parasites that adhered more to CSA than those from multigravidae. Data from this study further emphasize the specificity of CSA adhesion and VAR2CSA expression by parasites responsible for pregnancy malaria, while drawing attention to the phenotypic complexity of infections occurring early in pregnancy as well as in multigravidae.
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PMID:Dynamics in the cytoadherence phenotypes of Plasmodium falciparum infected erythrocytes isolated during pregnancy. 2490 23

Infections with hepatitis B virus (HBV) and hepatitis C virus (HCV) are major causes of morbidity and mortality globally, primarily because of sequelae of chronic liver disease including cirrhosis and hepatocellular carcinoma. The risks for HBV and HCV transmission via blood transfusions have been described previously and are believed to be higher in countries in sub-Saharan Africa. Reducing the risk for transfusion-transmitted human immunodeficiency virus (HIV), HBV, and HCV infection is a priority for international aid organizations, such as the U.S. President's Emergency Plan for AIDS Relief (PEPFAR), the Global Fund to Combat HIV/AIDS, Malaria, and Tuberculosis, and the World Health Organization (WHO). Over the last decade, PEPFAR and the Global Fund have supported blood safety programs in many sub-Saharan African countries with heavy burdens of HIV and acquired immunodeficiency syndrome (AIDS), hepatitis, malaria, and maternal mortality. This report summarizes HBV- and HCV-related surveillance data reported by the blood transfusion services of WHO member states to WHO's Global Database on Blood Safety (GDBS) (4). It also evaluates the performance of blood safety programs in screening for HBV and HCV in 38 sub-Saharan Africa countries. Selected GDBS indicators were compared for the years 2000 and 2004 (referred to as the 2000/2004 period) and 2010 and 2011 (referred to as the 2010/2011 period). From 2000/2004 to 2010/2011, the median of the annual number of units donated per country increased, the number of countries screening at least 95% of blood donations for HBV and HCV increased, and the median of the national prevalence of HBV and HCV marker-reactive blood donations decreased. These findings suggest that during the past decade, more blood has been donated and screened for HBV and HCV, resulting in a safer blood supply. Investments in blood safety should be continued to further increase the availability and safety of blood products in sub-Saharan Africa.
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PMID:Progress toward prevention of transfusion-transmitted hepatitis B and hepatitis C infection--sub-Saharan Africa, 2000-2011. 2505 84

Testosterone (T) is known to induce persistent susceptibility to Plasmodium chabaudi malaria. Pathogens recognizing Toll-like receptors (TLRs), though potentially important against malaria, have not yet been examined for their T-sensitivity. Here, we investigate effects of T and P. chabaudi on mRNA expression and promoter DNA methylation of Tlr1-9 genes in the liver of female C57BL/6 mice. These are treated with T or vehicle for 3 weeks, and then treatment is discontinued for 12 weeks, before challenging with P. chabaudi for 8 days. Our data reveal that T induces a 9.1-fold downregulation of Tlr6 mRNA and 6.3-fold upregulation of Tlr8 mRNA. Blood-stage infections induce significant increases in mRNA expression of Tlr1, 2, 4, 6, 7, and 8 varying between 2.5-fold and 21-fold in control mice. In T-pretreated mice, these Tlr genes are also significantly responsive to infections. However, the malaria-induced upregulations of the relative mRNA expressions of Tlr6 and Tlr8 are 5.6-fold higher and 6.5-fold lower in T-pretreated mice than in control mice. Infections induce a massive DNA down-methylation of the Tlr6 gene promoter in control mice, which is still more pronounced in T-pretreated mice, while significant changes are not detectable for the DNA methylation status of the Tlr8 promoter. Our data support the view that hepatic expression of Tlr6, but not that of Tlr8 is epigenetically controlled, and that the dysregulations of Tlr6 and Tlr8 critically contribute to T-induced persistent susceptibility to P. chabaudi malaria, possibly by dys-balancing responses of TLR6-mediated pathogen recognition and TLR8-mediated generation of anti-malaria "protective" autoimmunity.
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PMID:Testosterone persistently dysregulates hepatic expression of Tlr6 and Tlr8 induced by Plasmodium chabaudi malaria. 2505 43

Birds can host a wide spectrum of pathogens. While in the air, sea or on the ground they can carry ticks on their skin and microbes in the intestines (campylobacter, salmonella) or blood (viruses, borrelia spirochetes and protozoa). The high body temperature favors the growth of Borrelia garinii (causing neuroborreliosis), Campylobacterjejuni and certain viruses. Viral infections carried by birds include West Nile-virus and Japanese encephalitis, Newcastle disease and flu. Less studied are infections of the birds themselves, like bird malaria. Infections can be prevented by avoiding contacts to feces, vector animals (ticks and mosquitoes) and by hygienic food processing.
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PMID:[Birds as carriers of human disease]. 2509 76


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