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Shigella infection

Category: Illness or disabilities

Type

Involuntary

Introduction and description

 

Shigella is a genus of Gram-negative, facultative anaerobic bacteria closely related to Salmonella and Escherichia.  Shigella infection is thus, superficially at least, a bacterial infection.

The causative agent of human shigellosis, it is only naturally found in humans and apes.  During infection, it typically causes Dysentry. Shigella is one of the leading bacterial causes of diarrhoea worldwide.

As of 2006, the WHO reported that Shigella causes about 165 million cases of severe dysentery, with a million resulting in death each year, mostly among children in the developing world.  Africa and South Asia are the two regions with the highest levels of diarrhoea-related morbidity and mortality worldwide.

Symptoms

Symptoms can take as long as a week to appear, but most often begin two to four days after ingestion. Symptoms usually last for several days, but can last for weeks.

Diarrhoea and sickness

The most common symptoms of shigella infection are diarrhoea, fever, nausea, vomiting, stomach cramps, and flatulence. It is also commonly known to cause large and painful bowel movements.  All are symptoms of a pathogen having entered the body and the immune system trying to expel it via diarrhoea or by vomiting.

Dysentry

The stool may contain mucus, or pus.  Shigella may cause dysentery - an inflammation of the intestine causing diarrhoea with blood.  Again there may be fever, abdominal pain, and rectal tenesmus (a feeling of incomplete defecation).

This symptom is a sign that something - a pathogen of some sort is attacking the walls of the intestine causing it to bleed. This attack results in the destruction of the epithelial cells of the intestinal mucosa in the cecum and rectum.  It is known the pathogen invades the host through the M-cells interspersed in the gut epithelia of the small intestine.

Seizures

In rare cases, young children may have seizures.  This symptom is either a sign that the pathogen has entered the blood stream crossed the blood brain barrier and entered the brain; or that the person is suffering from severe dehydration caused by continual fluid loss.

Anaemia and kidney failure

 

Some strains of the bacteria produce the enterotoxin Shiga toxin. Detection of Shiga toxin can be followed by anaemia caused by destruction of red blood cells, acute kidney failure (uremia), and a low platelet count (thrombocytopenia). It predominantly, but not exclusively, affects children. Most cases are preceded by an episode of bloody diarrhoea. It is now the most common cause of acquired acute renal [kidney] failure in childhood. It is worth noting that these same symptoms can also be caused by E. coli O157:H7, Campylobacter and a variety of viruses.

We should not be too hasty about attributing the cause to Shiga toxin.  If we leave it at 'the pathogen' then we can say that a pathogen of some sort has attacked the walls of the intestine causing it to bleed.  Then once it has broken through the wall it  has entered the blood stream and migrated to the kidney.

Arthritis

Shigella is also implicated as one of the pathogenic causes of reactive arthritis worldwide.  In effect, the pathogen has migrated this time to the joints.

Reactive arthritis is classically seen following infection with enteric pathogens such as Yersinia, Salmonella, Campylobacter and Shigella. Inflammatory arthritis has also been described following other enteric infection with organisms such as Clostridium difficile, Brucella and Giardia. Furthermore, arthritis is seen in Whipple's disease, caused by the actinomycete Tropheryma whippelii. …..Recent work exploring evidence for traffic of pathogenic organisms to the joint is highlighted. A practical approach to the diagnosis and management of the condition is then formulated based, where possible, on clinical trial evidence.  PMID: 12787523

The implication from this is that the pathogen can actually get anywhere once it has entered the blood stream, it is just that the brain, kidneys and joints are known sites of further infection.

Causes

 

Shigella species are classified by four serogroups:

  • Serogroup A: S. dysenteriae (15 serotypes)
  • Serogroup B: S. flexneri (six serotypes)
  • Serogroup C: S. boydii (19 serotypes)
  • Serogroup D: S. sonnei (one serotype)

Groups A–C are physiologically similar; S. sonnei (group D) can be differentiated on the basis of biochemical metabolism assays. Three Shigella groups are the major disease-causing species:

  • S. flexneri is the most frequently isolated species worldwide, and accounts for 60% of cases in the developing world;
  • S. sonnei causes 77% of cases in the developed world, compared to only 15% of cases in the developing world; and
  • S. dysenteriae is usually the cause of epidemics of dysentery

Phylogenetic studies indicate Shigella is more appropriately treated as a subgenus of Escherichia, and that certain strains generally considered E. coli are better placed in Shigella. There are a number of supposed E. coli strains that are at least in part actually more closely related to Shigella than to the "typical" E. coli.

Treatment

Bed rest, adequate dehydration and food to help the immune system, if the person is able to take solids.  We have included an observation showing Dr Duke's analysis of plants able to combat shigella, but first you need to read the following, as it may not be the right thing to use this approach.

Shigella and the Intestine

The healthy human intestine is colonized by as many as 1014 bacteria belonging to more than 500 different species forming a microbial ecosystem of unsurpassed diversity, termed the microbiota.

The microbiota's various bacterial members engage in a physiological network of cooperation and competition within several layers of complexity. Within the last 10 years, technological progress in the field of next-generation sequencing technologies has tremendously advanced our understanding of the wide variety of physiological and pathological processes that are influenced by the commensal microbiota.

An increasing number of human disease conditions, such as inflammatory bowel diseases (IBD), type 2 diabetes, obesity, allergies and colorectal cancer are linked with altered microbiota composition.

Moreover, a clearer picture is emerging of the composition of the human microbiota in healthy individuals, its variability over time and between different persons and how the microbiota is shaped by environmental factors (i.e., diet) and the host's genetic background.

A general feature of a normal, healthy gut microbiota can generate conditions in the gut that disfavor colonization of enteric pathogens. This is termed colonization-resistance (CR). Upon disturbance of the microbiota, CR can be transiently disrupted, and pathogens can gain the opportunity to grow to high levels. This disruption can be caused by

  • exposure to antibiotics
  • changes in diet
  • application of probiotics
  • drugs [pharmaceuticals] , and
  • a variety of diseases.

Breakdown of CR can boost colonization by intrinsic pathogens or increase susceptibility to infections. One consequence of pathogen expansion is the triggering of inflammatory host responses and pathogen-mediated disease. Interestingly, human enteric pathogens are part of a small group of bacterial families that belong to the Proteobacteria:

  • the Enterobacteriaceae (E. coli, Yersinia spp., Salmonella spp., Shigella spp.),
  • the Vibrionaceae (Vibrio cholerae) and the
  • Campylobacteriaceae (Campylobacter spp.).

In general, members of these families (be it commensals or pathogens) only constitute a minority of the intestinal microbiota.

Commensalism, in ecology, is a class of relationships between two organisms where one organism benefits from the other without affecting it.  Enteric here means native to the gastrointestinal tract - a natural part of the flora.  So what is being said here is that there are Shigella bacteria in our intestines already and they not only do no harm, they are a fundamental part - albeit a small part - of its working.

 Bacteriophages

 Shigella bacteria are yet another group of bacteria that can be inhabited by bacteriophage.  A bacteriophage  is a virus that infects and replicates within a bacterium. The term is derived from "bacteria" and the Greek: φαγεῖν (phagein), "to devour". The word devour is misleading.  Generally speaking, the viruses do not actually harm their host, but co-exist, using them like a Trojan horse to enter other organisms.  In effect the bacteria, perhaps being one less likely to be attacked by the immune system because it is one naturally found in the host, is used as a hiding place in the host – a place in which the virus can breed and spread its little phages.

The description in the science section needs to be read in order to fully understand phages.  But it is clear from the evidence, that in quite a number of cases we are attributing disease to the bacteria, when the true culprit is the phage.  In this case antibiotics simply will not work.  One bacteria in which this applies is the Streptococci bacteria.  It looks as though Shigella may be another.

There are a number of reasons for suspecting the virus phage as the cause of illness rather than the bacteria.  In the first place, Shigella is being classified as ‘antibiotic resistant’, but it is possible that the bacteria is being killed but the virus with its symptoms remains.  Secondly the viruses are truly tiny and would easily be overlooked as a possible pathogen in any analysis

Siphoviridae bacteriophage (phage), pSf-2, infecting S. flexneri was isolated from Geolpocheon stream in Korea. Morphological analysis by transmission electron microscopy revealed that pSf-2 has a head of about 57 ± 4 nm in diameter with a long tail of 136 ± 3 nm in length and 15 ± 2 nm in width.  ……Genome sequence analysis of pSf-2 and comparative analysis with the homologous T1-like Shigella phages, Shfl1 and pSf-1, revealed that pSf-2 is a novel T1-like Shigella phage. PMID: 26612033

Thirdly, it is known that at least one disease – the arthritis mentioned above follows on from infection with the bacteria, but the bacteria themselves cannot be found.

The role of shiga toxins

Shigella bacteria infected by phages produce shiga toxins.  So from this comes the question - is the bacteria producing the toxin to get rid of the bacteriophage, or is it a general purpose toxin, produced by the phages that acts like a sort of smoke screen?

It is known, albeit in the case of sheep, that shiga toxin can act against multiple viruses, but unfortunately this still tells us nothing.  The toxin may still be produced by the bacteria and be a general antiviral, or it may be produced by the phage in order to reduce the competition.

Healthy ruminants carry intestinal Shiga toxin (Stx)-producing Escherichia coli (STEC). Stx has antiviral activities in vitro and STEC numbers correlate with reduced early viremia in sheep experimentally infected with bovine leukemia virus (BLV). This study assessed the impact of intestinal STEC on BLV-induced disease for one year post-BLV-challenge. High STEC scores (CFU/g feces x frequency of STEC-positive samples) correlated with good health, whereas poor weight gain, distress, and tumor development occurred only among animals with low STEC scores. STEC carriage was associated with increased percentages of B cells in peripheral blood.  PMID:  19043312

 

What might help here is to know which organism really produces the toxin and from the analysis below it is clearly the bacteria, it has the genes to do so.  This rather implies it was designed to produce the toxin, almost like a weapon of last resort in its battle with the phages.  It cannot turn the weapon on itself, but once the phages are released the toxins are released :

Shiga toxins (Stx) are commonly produced by Shigella dysenteriae serotype 1 and Stx-producing Escherichia coli. However, the toxin genes have been detected in additional Shigella species. We recently reported the emergence of Stx-producing Shigella in travelers in the United States and France who had recently visited Hispaniola (Haiti and the Dominican Republic). In this study, we confirm this epidemiological link by identifying Stx-producing Shigella from Haitian patients attending clinics near Port-au-Prince. We also demonstrate that the bacteriophage encoding Stx is capable of dissemination to stx-negative Shigella species found in Haiti, suggesting that Stx-producing Shigella may become more widespread within that region. PMID:  26484357

 ........ because the phages are spreading.  The main thing we need to understand is that the battle is highly complex - highly complex

Intelligent Virus Tricks - Dr John Lieff

One system involves the bacteria making two different toxins, one that is stable and one that is not stable. When stress occurs, such as a viral infection, the antitoxic deteriorates and the toxin either kills the bacteria or makes it dormant.............Another system uses two proteins. The first senses the infection of virus and the second creates a hole in the membrane creating a loss of ATP energy in the cell. This stops the bacteria and also the virus. .......Research into fermented dairy products has found 23 different systems where bacteria kill itself in the process of exterminating the virus infection. These involve many completely different mechanisms affecting the process of DNA, RNA and proteins production in the cells.  Some viruses sidestep elements of this process. They keep the bacteria alive by manufacturing a molecule that replaces the bacterial antitoxin function, thereby eliminating death of the cell and allowing the virus to continue.

 

One final point.  Phages the size of those which infect the shigella bacteria are equivalent in size to nanoparticles and nanoparticles are known to be able to cause genetic mutation.

....DNA damage occurs chemically or physically by nanomaterials. Chemical and physical damage are associated with point mutation by free radicals and double strand brake, respectively. The failure of DNA repair and accumulation of mutations might occur when inflammation is prolonged, and finally normal cells could become malignant. These free radicals can not only damage cells but also induce signaling molecules containing immunoreaction. Nanoparticles and asbestos also induce the production of free radicals. .... Taken together,... a variety of diseases [may be] induced by nanomaterials. PMID: 25097864

a somewhat terrifying picture now looms before us.  In our zeal to treat everything with antiobiotics at every opportunity, we could be killing innocent bacteria and releasing the largest epidemic of nanoparticle size viruses the world has ever seen.  Enough to cause death and mutation on a quite catastrophic level.

Intelligent Virus Tricks - Dr John Lieff

The complex intelligent battle between bacteria and the phage virus determines much of what occurs on the earth, these being the two most numerous life forms. Half of the ocean bacteria are killed each day in this battle; the White Cliffs of Dover, made of dead microbes, are a small remnant of the combat. Bacteria have developed a vast arsenal of weapons to survive being surrounded by thousands of phage virus at all times. Phage viruses, equally intelligent, have developed many counter moves. All of these weapons are based on stimulating, editing and manipulating genes to make new proteins with unique shapes. It is difficult to imagine how such complex large molecules that interact in extremely complex signaling pathways can be redesigned rapidly in warfare.These methods developed by bacteria and viruses have in many ways defined evolution. - read more at: this LINK

 

 ........... the phages are not necessarily the good guys.

References and further reading

  • Infect Genet Evol. 2015 Nov 23;37:150-157. doi: 10.1016/j.meegid.2015.11.022. [Epub ahead of print]  Comparative analysis of the Shiga toxin converting bacteriophage first detected in Shigella sonnei.  Tóth I1, Sváb D2, Bálint B3, Brown-Jaque M4, Maróti G5.  PMID:  26616675
  • Microbiol Spectr. 2015 Jun;3(3). doi: 10.1128/microbiolspec.MBP-0008-2014.  The Roles of Inflammation, Nutrient Availability and the Commensal Microbiota in Enteric Pathogen Infection.  Stecher B.
  • Open Forum Infect Dis. 2015 Sep 19;2(4):ofv134. doi: 10.1093/ofid/ofv134. eCollection 2015.  Stx-Producing Shigella Species From Patients in Haiti: An Emerging Pathogen With the Potential for Global Spread.  Gray MD1, Leonard SR2, Lacher DW2, Lampel KA2, Alam MT3, Morris JG Jr4, Ali A3, LaBreck PT1, Maurelli AT1.
    • 1Department of Microbiology and Immunology , Uniformed Services University of the Health Sciences , Bethesda.
    • 2US Food and Drug Administration, Center for Food Safety and Nutrition , Laurel, Maryland.
    • 3University of Florida, Emerging Pathogens Institute, ; Department of Environmental and Global Health, College of Public Health and Health Professions , University of Florida , Gainesville.
    • 4University of Florida, Emerging Pathogens Institute.

Pictures

All the pictures on this page came from the game Goblins and Gnomes.  The game is from  Hearthstone: Heroes of Warcraft and is an online card game developed by Blizzard Entertainment. It is free-to-play with optional purchases to acquire additional cards and access content more quickly. The game was announced at the Penny Arcade Expo in March 2013 and released on March 11, 2014. 

The archetype of the bacteria is a gnome, the archetype of a virus is a goblin.

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