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Guinea Worm Disease

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Humans are hosts to nearly 300 species of parasitic worms and over 70 species of protozoa, some derived from our primate ancestors and some acquired from the animals we have domesticated or come into contact with during our history (History of human parasitology. Clin Microbiol Rev 2002 15: 595-612). The best-documented parasitic disease known from ancient times is caused by the nematode worm Dracunculus medinensis. The earliest description is from an Egyptian papyrus from 1500 BC that refers to both the nature of the infection and to techniques for removing the worm. Confirmation of the presence of this worm in ancient Egypt comes from the finding of a well-preserved worms in Egyptian mummies. Dracunculiasis, or Guinea worm disease, is one of the few diseases unambiguously described in the Bible, and most parasitologists accept that the “fiery serpents” that struck down the Israelites in the region of the Red Sea after the Exodus from Egypt somewhere between 1250 to 1200 BC were actually Guinea worms.

The adult worms live in the subcutaneous connective tissues of their victims, from which the females emerge to release thousands of larvae into water, where they are taken up by intermediate hosts, tiny aquatic crustaceans called Cyclops. In these hosts they mature into infectious larvae that infect humans when the crustaceans are accidentally swallowed in contaminated drinking water. On maturity, the large female worm, up to nearly a metre in length, protrudes from the skin, usually of the leg, and causes intense inflammation and irritation. The effects of the disease are crippling. Its victims develop large ulcers, usually in the lower leg. The ulcers swell, sometimes to the size of a tennis ball, and burst, releasing the spaghetti-like parasitic worm. Victims experience a pain so excruciating that they say it feels as if their leg is on fire. The searing pain compels people to jump into water, often the community’s only source of drinking water, to relieve the pain. When the infected person immerses his or her leg in the water, the worm in the leg releases thousands of larvae. The larvae are then ingested by Cyclops that live in the water. Thus the cycle begins again - when people drink the water, they are in effect drinking in the disease.

The most common way to treat Guinea worm disease involves wrapping the worm around a stick. This treatment has been employed for millennia and may have inspired the Rod of Asclepius which historically has symbolized the medical profession. As the adult worm begins to emerge from the patient’s skin, it is wound around a stick, then further extracted by a few centimeters per day. This slow process can take days or even weeks, but it is required to avoid breakage and leaving behind a portion of the worm. Leaving a portion of the dead worm remain within the host’s body increases the risk of infection, and can trigger immune responses resulting in pain and swelling. In many countries, a broken worm is immediately removed surgically, or the worm can be excised surgically from the very beginning if health care facilities are available. Antihelminthic drugs such as metronidazole or thiabendazole are sometimes used in conjunction with physical extraction. However, one study found that antihelminthic therapy was associated with aberrant migration of worms, resulting in infection in areas other than the lower extremity.

Dracunculiasis is a classic example of a neglected tropical disease, a symptom of poverty and disadvantage. Those most affected are the poorest populations often living in remote, rural areas, urban slums or in conflict zones. With little political voice, neglected tropical diseases have a low profile and status in public health priorities. In 1997 the World Health Assembly pledged to completely eradicate Guinea worm disease. This is no small task, but there are several factors which make eradication a possibility. Dracunculiasis is the first parasitic disease targeted for eradication because:

• Diagnosis is easy and unambiguous (presence of an emerging adult worm).
• The transmission agent, Cyclops, is not a mobile vector as is a mosquito.
• The incubation period in both Cyclops and humans is of limited duration.
• Interventions are effective, low cost, and relatively simple to implement.
• The disease has a limited geographic distribution and is seasonal in nature.
• Success in eliminating the disease has been demonstrated in several countries in Asia and the Middle East.
• There is no known animal reservoir.

Is Dracunculiasis eradication close? In 2007 the WHO announced that Guinea worm disease now affects around 25,000 people in nine countries, compared with an estimated 3 million people were infected in over 20 countries in the early 1980s. Twelve countries were declared Guinea worm-free in early March. If progress continues at this rate, the disease could be eradicated in less than two years. It is probable that complete eradication will take quite a few years yet, although it should be possible to eliminate the disease from seven countries in a couple of years, leaving only two endemic countries, Sudan and Ghana (Dracunculiasis eradication by 2009: will endemic countries meet the target? Tropical Medicine & International Health 2007 12: 1403-1408). One lesson to be drawn from the problems of local ownership and the experience of cash rewards is that there are dangers in throwing money at the problem. While the eradication initiative badly needs additional resources, it needs them at such a level and managed in such a way that they do not distort the priorities of the health care system, or exceed the capacity of local staff to manage them. The amounts needed are not large, but their continuity and flexibility is important. Given the highly seasonal transmission of dracunculiasis, the resources must be available at very specific times of the year, which is not always achieved. In spite of the difficulties, complete worldwide eradication of this ancient disease is drawing nearer.

Marine mimivirus relatives are large algal viruses

Acanthamoeba polyphaga mimivirus is the largest known ds-DNA virus and its 1.2 Mb-genome sequence has revealed many unique features. Mimivirus occupies an independent lineage among eukaryotic viruses and its known hosts include only species from the Acanthamoeba genus. The existence of Mimivirus relatives was first suggested by the analysis of the Sargasso Sea metagenomic data. We now further demonstrate the presence of numerous “mimivirus-like” sequences using a larger marine metagenomic data set. We also show that the DNA polymerase sequences from three algal viruses (CeV01, PpV01, PoV01) infecting different marine algal species (Chrysochromulina ericina, Phaeocystis pouchetii, Pyramimonas orientalis) are very closely related to their homolog in Mimivirus. The results suggest that the numerous mimivirus-related sequences identified in marine environments are likely to originate from diverse large DNA viruses infecting phytoplankton. Micro-algae thus constitute a new category of potential hosts in which to look for new species of Mimiviridae.

Marine mimivirus relatives are probably large algal viruses
Virol J. 2008 5:12

Related:

• Marvellous mimivirus
• DNA Viruses

Magnetic Bacteria

Magnetic or “magnetotactic” bacteria were first discovered in the 1960s, and naturally organize themselves in the direction of Earth’s magnetic field, as shown in this video:

Video by Melbynfm

Inside these bacteria there is a row of iron-containing crystals aligned with the long axis of the cell, giving them the equivalent of an internal magnetic compass needle (Molecular mechanisms of magnetosome formation. Ann Rev Biochem 2007 76: 351-66). Such bacteria can sense and align themselves relative to the earth’s magnetic field. Magnetotactic bacteria are major constituents of many natural microbial communities, especially in aquatic habitats. There is a broad range of shapes and groups of magnetic bacteria. However, cultivation of these organisms in the laboratory is often difficult and only few strains of magnetotactic bacteria have been isolated in pure culture, a tiny minority of the vast diversity of naturally occurring populations from largely unexplored natural habitats such as the marine environment.

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So why would bacteria want to be magnetic? Leaving aside the possibility that they are magnetic by accident, e.g. as a consequence of some metabolic byproduct, the truth is that we really don’t know the reason. However, the most likely explanation lies not in north-south alignment, but in up and down. The magnetotactic bacteria we know about require low but very precise levels of oxygen to survive, and must live in sediments where the oxygen concentration is just right for their needs. Over much of the globe, the Earth’s magnetic field actually points down towards the centre of the planet, so by following these lines of magnetic flux, they are able to ensure that they bury themselves in the sediment, which is exactly where they want to be. Thus the majority of magnetotactic in the Northern Hemisphere are north seeking, and those in the Southern Hemisphere are south seeking.

So, just one of nature’s curiosities then? Possibly not. One of the hottest areas of scientific research at present is nanotechnology, the fabrication of devices with dimensions on an atomic or molecular scale. By understanding how these bacteria construct the internal magnetosomes which give them their unique properties, we may be able to learn how to use this knowledge in a range of engineering and biotechnological applications (Molecular analysis of magnetotactic bacteria and development of functional bacterial magnetic particles for nano-biotechnology. Trends Biotechnol 2007 25: 182-8). Computer the size of a grain of sand anyone?

Biofuels from algae

Oil production from algae claimed to be 3-10 times more efficient than producing biofuels from corn:

The Great Indoors

We spend most of our lives in indoor environments and are exposed to microbes present in these environments. Hence, knowledge about this exposure is important for understanding how it impacts on human health. However, the bacterial flora in indoor environments has been only fragmentarily explored and mostly using culture methods. The application of molecular methods previously utilised in other environments has resulted in a substantial increase in our awareness of microbial diversity. The composition and dynamics of indoor dust bacterial flora were investigated in two buildings over a period of one year. Four samples were taken in each building, corresponding to the four seasons, and 16S rDNA libraries were constructed.

All libraries were dominated by Gram-positive sequences, with the most abundant phylum being Firmicutes. Four OTUs having high similarity to Corynebacterium, Propionibacterium, Streptococcus and Staphylococcus sequences were present in all samples. The most abundant of the Gram-negative OTUs were members of the family Sphingomonadaceae, followed by Oxalobacteraceae, Comamonadaceae, Neisseriaceae and Rhizobiaceae. The relative abundance of alpha- and betaproteobacteria increased slightly towards summer at the expense of firmicutes. The proportion of firmicutes and gammaproteobacteria of the total diversity was highest in winter and that of actinobacteria, alpha- and betaproteobacteria in spring or summer, whereas the diversity of bacteroidetes peaked in fall. A statistical comparison of the libraries revealed that the bacterial flora of the two buildings differed during all seasons except spring, but differences between seasons within one building were not that clear, indicating that differences between the buildings were greater than the differences between seasons. This work demonstrates that the bacterial flora of indoor dust is complex and dominated by Gram-positive species. The dominant phylotypes most probably originated from users of the building. Seasonal variation was observed as proportional changes of the phyla and at the species level. The microflora of the two buildings investigated differed statistically and differences between the buildings were more pronounced than differences between seasons.

Diversity and seasonal dynamics of bacterial community in indoor environment
BMC Microbiology 2008, 8: 56

Genetic and environmental factors affect gene expression in yeast

Individuals frequently encounter different environmental conditions, and the physiological and behavioral responses to these conditions can depend on an individual’s genetic makeup. This phenomenon is known as gene–environment interaction. For example, individuals who are infected with the Plasmodium falciparum parasite are susceptible to malaria, but not if they carry the sickle-cell allele of hemoglobin. The general properties of gene–environment interaction are poorly understood, and a better understanding is essential if individuals are to make informed health choices guided by their genomic information. A new paper just published in the open-access journal PLoS Biology shows that there is a balance between inherited genes and the environment in determining thousands of traits in yeast.

The authors investigated gene–environment interaction on a genomic level, characterizing its role in over 4,000 traits at once by investigating natural variation in yeast gene expression. They compared lab and vineyard strains of yeast growing in two conditions (glucose and ethanol as carbon sources) in which they adopt two different metabolic states: fermentation and aerobic respiration, respectively. This showed that gene–environment interaction is a common phenomenon, and provides detailed molecular examples of these interactions.

As we approach the age of personal genomics, in which each of us knows something about the genetic variations we carry, it is important to understand how genes and the environment interact in order to draw medically sound conclusions from the information available e.g. whether exercise can reduce risks that are increased because of a genetic predisposition towards a certain illness. The phenomenon of gene/environment interaction has been documented before, that the environment affects the ways it genes are expressed so that genes that are on in one condition may be downregulated or switched off in other environments. What the new research adds is the ability to study thousands of gene expression patterns simultaneously, to understand the general properties of these previously poorly understood interactions. The expression of many genes is under the control of other genes. This paper shows that the environment often has a bigger effect on these regulated genes than on ones that are switched on and off by other, more direct mechanisms. Intriguingly, sometimes a control gene that positively affects another gene in one environment may have the opposite effect in another environment.

Gene environment interaction in yeast gene expression. PLoS Biol 6(4): e83

The Mummy

The environmental persistence of Mycobacterium tuberculosis is subject to speculation. However, the reality that infected postmortem tissues can be a danger to pathologists and embalmers has worrisome implications. A few experimental studies have demonstrated the organism’s ability to withstand exposure to embalming fluid and formalin. Recently, a failure was reported in an attempt to resuscitate an original isolate of Robert Koch to determine the lifetime of the tubercle bacillus. This study considers a historical approach to determine persistence under favorable environmental conditions and asks whether acid-fast forms observed in tissues of 300-year-old Hungarian mummies can be resuscitated. Finding organisms before the advent of antibiotics and pasteurization may yield valuable genetic information. Using various media modifications, as well as guinea pig inoculation, an attempt was made to culture these tissues for M. tuberculosis. In addition, a resuscitation-promoting factor, known to increase colony counts in high G+C bacteria, was applied to the cultures. Although an occasional PCR-positive sample was detected, no colonies of M. tuberculosis were obtained. Our results may indicate that the life span of the tubercle bacillus is less than a few hundred years, even though in the short run it can survive harsh chemical treatment.

Attempts to revive Mycobacterium tuberculosis from 300-year-old human mummies
FEMS Microbiology Letters 09 Apr 2008

Metagenomic Analysis of Human Diarrhoea

Diarrhoea is one of the leading infectious causes of death worldwide with an estimated 1.8 million deaths annually, primarily in young children in developing countries. There are many known causes of diarrhoea; however, the causes of up to 40% of the cases are still unknown. One possibility is that viruses that we currently do not know about are responsible for these cases. The advent of metagenomic sequencing has enabled systematic and unbiased characterization of microbial populations; thus, metagenomic approaches have the potential to define the spectrum of viruses, including novel viruses, present in stool during episodes of acute diarrhoea. The detection of novel or unexpected viruses would then enable investigations to assess whether these agents play a causal role in human diarrhoea.

This paper uses an experimental strategy termed “micro-mass sequencing” to systematically identify viruses present in stool from a number of patients suffering from diarrhoea. Using this methodology we detected known enteric viruses as well as multiple sequences from putatively novel viruses with only limited sequence similarity to viruses in GenBank. Sequences from a number of novel viruses were detected, some which differed quite significantly from any previously described virus. These new viruses may or may not be responsible for causing diarrhoea. Future studies will specifically address the potential of these viruses to cause human disease. One implication of this study is that there are likely to be many more unknown viruses that can be identified in this fashion. Furthermore, by studying these viruses, we will come to a more complete understanding of the role viruses play in diarrhoea. Ultimately, this may lead to the development of therapeutics and/or vaccines that decrease the disease burden of diarrhoea.

Metagenomic Analysis of Human diarrhoea: Viral Detection and Discovery
PLoS Pathog 2008 4(2): e1000011