MicrobiologyBytes

Malaria is one of the most common infectious diseases in the world and one of the greatest global public health problems. The Plasmodium falciparum parasite causes approximately 500 million cases each year and over one million deaths in sub-Saharan Africa. More than 40% of the world’s population is at risk of malaria. The parasite is transmitted to people through the bites of infected mosquitoes. These insects inject a life stage of the parasite called sporozoites, which invade human liver cells where they reproduce briefly. The liver cells then release merozoites (another life stage of the parasite), which invade red blood cells. Here, they multiply again before bursting out and infecting more red blood cells, causing fever and damaging vital organs. The infected red blood cells also release gametocytes, which infect mosquitoes when they take a blood meal. In the mosquito, the gametocytes multiply and develop into sporozoites, thus completing the parasite’s life cycle. Malaria can be prevented by controlling the mosquitoes that spread the parasite and by avoiding mosquito bites by sleeping under insecticide-treated bed nets. Effective treatment with antimalarial drugs also helps to decrease malaria transmission.

In 1998, the World Health Organization and several other international agencies launched Roll Back Malaria, a global partnership that aims to reduce the human and socioeconomic costs of malaria. Targets have been continually raised since this time and have culminated in the Roll Back Malaria Global Malaria Action Plan of 2008, where universal coverage of locally appropriate interventions is called for by 2010 and the long-term goal of malaria eradication again tabled for the international community. For malaria control and elimination initiatives to be effective, financial resources must be concentrated in regions where they will have the most impact, so it is essential to have up-to-date and accurate maps to guide effort and expenditure. In 2008, researchers of the Malaria Atlas Project constructed a map that stratified the world into three levels of malaria risk: no risk, unstable transmission risk (occasional focal outbreaks), and stable transmission risk (endemic areas where the disease is always present). Now, researchers extend this work by describing a new evidence-based method for generating continuous maps of P. falciparum endemicity within the area of stable malaria risk over the entire world’s surface. They then use this method to produce a P. falciparum endemicity map for 2007. Endemicity is important as it is a guide to the level of morbidity and mortality a population will suffer, as well as the intensity of the interventions that that will be required to bring the disease under control or additionally to interrupt transmission.

The researchers identified nearly 8,000 surveys of P. falciparum parasite rates (Pf PR; the percentage of a population with parasites detectable in their blood) completed since 1985 that met predefined criteria for inclusion into a global database of PfPR data. They then used ‘‘model-based geostatistics’’ to build a world map of P. falciparum endemicity for 2007 that took into account where and, importantly, when and all these surveys were done. Predictions were comprehensive (for every area of stable transmission globally) and continuous (predicted as a endemicity value between 0% and 100%). The population at risk of three levels of malaria endemicity were identified to help summarize these findings: low endemicity, where PfPR is below 5% and where it should be technically feasible to eliminate malaria; intermediate endemicity where PfPR is between 5% and 40% and it should be theoretically possible to interrupt transmission with the universal coverage of bed nets; high endemicity is where PfPR is above 40% and suites of locally appropriate intervention will be needed to bring malaria under control. The global level of malaria endemicity is much reduced when compared with historical maps. Nevertheless, the resulting map indicates that in 2007 almost 60% of the 2.4 billion people at malaria risk were living in areas with a stable risk of P. falciparum transmission – 0.69 billion people in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africaþ), and 0.04 billion in the Americas. The people of the Americas were all in the low endemicity class. Although most people exposed to stable risk in CSE Asia were also in the low endemicity class (88%), 11% were in the intermediate class, and 1% were in the high endemicity class. By contrast, high endemicity was most common and widespread in the Africaþ region (53%), but with significant numbers in the intermediate (30%), and low (17%) endemicity classes.

The accuracy of this new world map of P. falciparum endemicity depends on the assumptions made in its construction and critically on the accuracy of the data fed into it, but because of the statistical methods used to construct this map, it is possible to quantify the uncertainty in the results for all users. Thus, this map (which, together with the data used in its construction, will be freely available) represents an important new resource that clearly indicates areas where malaria control can be improved (for example, Africa) and other areas where malaria elimination may be technically possible. In addition, planned annual updates of the global P. falciparum endemicity map and the PfPR database by the Malaria Atlas Project will help public health experts to monitor the progress of the malaria control community towards international control and elimination targets.

A world malaria map: Plasmodium falciparum endemicity in 2007. 2009 PLoS Med 6(3): e1000048
Efficient allocation of resources to intervene against malaria requires a detailed understanding of the contemporary spatial distribution of malaria risk. It is exactly 40 y since the last global map of malaria endemicity was published. This paper describes the generation of a new world map of Plasmodium falciparum malaria endemicity for the year 2007. A total of 8,938 P. falciparum parasite rate (PfPR) surveys were identified using a variety of exhaustive search strategies. Of these, 7,953 passed strict data fidelity tests for inclusion into a global database of PfPR data, age-standardized to 2–10 y for endemicity mapping. A model based geostatistical procedure was used to create a continuous surface of malaria endemicity within previously defined stable spatial limits of P. falciparum transmission. These procedures were implemented within a Bayesian statistical framework so that the uncertainty of these predictions could be evaluated robustly. The uncertainty was expressed as the probability of predicting correctly one of three endemicity classes; previously stratified to be an informative guide for malaria control. Population at risk estimates, adjusted for the transmission modifying effects of urbanization in Africa, were then derived with reference to human population surfaces in 2007. Of the 1.38 billion people at risk of stable P. falciparum malaria, 0.69 billion were found in Central and South East Asia (CSE Asia), 0.66 billion in Africa, Yemen, and Saudi Arabia (Africaþ), and 0.04 billion in the Americas. All those exposed to stable risk in the Americas were in the lowest endemicity class. The vast majority (88%) of those living under stable risk in CSE Asia were also in this low endemicity class; a small remainder(11%) were in the intermediate endemicity class; and the remaining fraction (1%) in high endemicity areas. High endemicity was widespread in the Africaþ region, where 0.35 billion people are at this level of risk. Most of the rest live at intermediate risk (0.20 billion), with a smaller number (0.11 billion) at low stable risk. High levels of P. falciparum malaria endemicity are common in Africa. Uniformly low endemic levels are found in the Americas. Low endemicity is also widespread in CSE Asia, but pockets of intermediate and very rarely high transmission remain. There are therefore significant opportunities for malaria control in Africa and for malaria elimination elsewhere. This 2007 global P. falciparum malaria endemicity map is the first of a series with which it will be possible to monitor and evaluate the progress of this intervention process.

Related:

• MicrobiologyBytes: Malaria
• Malaria, mosquitoes and the legacy of Ronald Ross
• New ways to beat malaria
• Researchers characterize potential protein targets for malaria vaccine
• Researchers Find Essential Proteins for Critical Stage of Malaria Transmission

We all live in an information rich, highly interconnected world, and the success of evolution can be measured in terms of how living organisms make sense of and respond to information. Past posts on quorum sensing are some of the most popular out of all the subjects I have covered on MicrobiologyBytes. Quorum sensing is the use of small molecules by bacteria to coordinate behavior by groups of individual cells and carry out decision-making processes.

Bacteria have evolved a number of communication systems which can be broadly described as contact-independent and contact-dependent signaling mechanisms. Quorum sensing is a contact-independent process since it involves transfer of secreted molecules called autoinducers. As autoinducer levels increase throughout a growing bacterial population, changes in gene transcription are triggered resulting in altered growth rates and group dynamics. There is an energy cost in producing these compounds and throwing them out of the cell, and in some conditions, the secretion of autoinducers may attract unwanted attention from competitors (Bacterial landlines: contact-dependent signaling in bacterial populations. Curr Opin Microbiol. Feb 24 2009). Contact-dependent signaling methods allow bacteria to carry out more direct, and possibly less costly, communication between cells – it’s the landline alternative to expensive cellphone bills.

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Known methods of contact-dependent signaling include C-signaling in Myxococcus xanthus which allows groups of cells to coordinate motile behavior. The process is mediated by a non-diffusable 17 kDa surface protein encoded by the csgA gene. Contact between neighboring myxobacteria initiates a p17-dependent signaling cascade resulting in expression of genes required for control of motility or for sporulation.

The Gram-positive soil bacterium Bacillus subtilis also undergoes a contact-dependent differentiation process as a means to produce dormant spores when faced with starvation. Under nutrient poor conditions, vegetative B. subtilis cells divide asymmetrically, forming a large mother cell and a smaller daughter cell called a forespore. Despite their intimate association, the mother cell and the forespore remain separated by two membranes and maintain distinct gene expression profiles. Endospore formation is an energy intensive process that is coordinated by multiple signaling pathways. Contact-dependent signaling plays an important role in allowing the cells to coordinate this process.

Contact-dependent inhibition also occurs in E. coli, where a single E. coli cell in the logarithmic phase of growth can use a CDI system to inhibit the growth of hundreds of susceptible target cells in mixed cultures, forcing them to enter a viable but non-replicating state. However, one of the first recognized instances of contact-dependent communication between bacteria was, arguably, conjugation mediated by sex (F) pili. Bacteria encode a large variety of other pilus types and adhesive molecules, many of which have been studied primarily with respect to their abilities to modulate bacteria–host cell interactions. However, it is feasible that some of these organelles also function in inter-bacterial communication. For example, recent studies indicate that several types of soil bacteria can express complex networks of electrically conductive pili known as nanowires.

Although quorum sensing has been getting all the attention recently, we have known about contact-dependent communication mechanisms in bacteria for far longer. Perhaps only now are we realizing how these complimentary systems might fit together and how they could shed light on the development of true multicellularity during evolution.

Related:

• Quorum Sensing in Bacteria: We Two Are One
• Pneumococcus: the quorum-sensing killer
• Quorum sensing in Serratia
• Cracking the cholera code

The process of bacterial pathogenesis involves complex and dynamic responses from both pathogen and host. While the host can mount an array of defense mechanisms to counteract an infection, bacterial pathogens utilize a number of virulence mechanisms to help them in their quest to invade, colonize, and infect. The expression pattern of virulence factors such as toxins, adhesions factors, enzymes, and others within the tissue determines the progression and outcome of infection. Deciphering the roles of bacterial effector proteins in the in vivo situation is essential to fully understand the infection process. The last decade has provided major technological developments, enabling dynamic live single cell imaging with high spatio-temporal resolution in vitro as well as in vivo. This review outlines current in vivo imaging techniques with primary focus on multiphoton microscopy, which was only recently adapted for real-time studies of bacterial infections within the host. Only few examples have been published to date, but they illustrate the huge potential real-time analysis of bacterial infections has to identify previously unknown aspects of tissue responses linked to bacterial pathogenesis.

Real-time live imaging to study bacterial infections in vivo. Curr Opin Microbiol. Jan 7 2009
In vitro studies have been essential to describe the molecular details of bacteria-host cell interactions in general and the functions of bacterial effector proteins in particular. Recent advancements in in vivo imaging techniques are facilitating the next logical step to visualize the dynamic infection process as it happens within the living host while analyzing the role of bacterial effector proteins in vivo. Data obtained from this emerging field of ’tissue microbiology’, combined with the massive knowledge base generated from research in ‘cellular microbiology’ will eventually provide a complete picture of the complex infection process.

Related:

• Tracking Lyme Disease in Living Hosts
• Imaging Poliovirus Entry in Live Cells

YouTube is such a great teaching tool, and lgines has used it to share a very useful video series on how to use a microscope.

Part 1:

Part 2:

Part 3:

Recently I’ve been using YouTube to give class feedback on assignments as well as to post my thoughts about various areas of education and educational technology. How do you use YouTube in your teaching?

Related:

• YouTube Nature Channel
• YouTube BioMed Central Channel
• YouTube BMJ Channel