Posts Tagged ‘ transmission ’

Leptospirosis

Introduction

Leptospirosis is a zoonotic disease caused by the bacterial genus Leptospira. Leptospires are spirochetes, a group of Gram-negative bacteria with long, thin, spiral structures and an internal flagella used for movement. The size of a typical leptospire is around 0.1μm wide and 6-20μm long. This narrow, helical structure enables them to burrow in to tissues, within tissues they may adopt a more spherical or granular appearance.

Etiology

The primary pathogenic strain of Leptospira is Leptospira interrogans, however there are also non-pathogenic strains such as Leptospira biflexa which is an environmental saprophyte (i.e. consumes dead organic matter).There are currently around >16 species of identified Leptospira.

Serovars & Serogroups

Serovars are groups of organisms, categorised depending on the antigens they present on their surface. Therefore if a number of organisms within a Leptospira species share the same antigens on their surface, they will be grouped together into one serovar. Differences in surface antigens occur within the same species for example, within the pathogenic L. interrogans species, around >250 serovars have been identified worldwide.

Serogroups are clusters of serovars, as there may be hundred of serovars within a species, it is useful to group those together which share similar properties. Important serovars of L. interrogans include:

  • Canicola (Primary reservoir host – Dog)
  • Icterohaemorrhagiae – (Rat, mouse)
  • Bratislava – (Rat, pig, horse)
  • Pomona – (Cattle, pig, skunk)
  • Grippotyphosa – (Rodents)
  • Hardjo – (Cattle)

Each serovar is not limited to its primary reservoir host however. They be transmitted to incidental hosts fairly easily. Incidental hosts include humans, dogs and cats as well as other domesticated animals.

Different serovars are also responsible for different clinical conditions which can range from abortion to haemorrhagic disease. An individual serovar may also cause different clinical conditions in different species, for example L.interrogans serovar hardjo causes abortion and still births in cattle, but in humans it can cause an influenza-like illness or liver/kidney diseases.

Epidemiology

Transmission Cycle

The transmission cycle of a typically Leptospira species is as follows:

  • Rodents shed Leptospira in their urine
  • Direct transmission of Leptospira to humans may occur at this stage
  • The urine contaminates the environment (e.g. soil, water) with Leptospira
  • Indirect transmission to humans may occur at this stage
  • Leptospira may be transmitted to other domestic animals via the environment
  • These animals may become infected and can shed Leptospira in their urine which can lead to direct transmission to humans or contaminate the environment as before

Rodents can acquire Leptospira from the urine contaminated environment, thus creating a cycle of transmission

Transmission via direct contact usually occurs by urine which contains the Leptospira organisms. However direct transmission may also occur via veneral or placental transfer as well as bite wounds or the ingestion of infected tissue material. Crowding of animals (such as in kennels or intensive farming) will enhance transmission of Leptospira. Animals which recover from the disease, may still be infected, thus making them carriers of Leptospira which can still be excreted chronically in their urine. This continues the spread of infection

Transmission via indirect contact can also occur. Methods of indirect transmission generally requires exposure to contaminated sources such as; soil, food, bedding or water sources. The bacteria enters susceptible hosts from the contaminated source via damaged skin or exposed mucous membranes such as in the nose, mouth, eyes etc. Leptospira remains viable in the environment (still able to cause infection) for months, this further enhances transmission.

Environmental Factors

The optimal habitat for Leptospira depends on their environment, if aquatic, optimal conditions are stagnant or slow moving waters. If terrestrial, a neutral or slightly alkaline soil pH is preferred. However, organisms may survive transiently in undiluted acidic urine. A typical temperature range of 0-25C is preferred, this often leads to seasonal fluctuations in the incidence of Leptospirosis.

Pathogenesis

Leptospira enters the host by penetrating mucous membranes via vunerable areas such as damaged skin, eyes, nose or the mouth. Their helical shape and flagella aids in tissue penetration. Upon entering the blood system, they begin to multiply rapidly. The presence of bacteria in the blood is called bacteraemia. They are then distributed around the body via the blood stream.

Once distributed around the body, they then further replicate in target organs and tissues (including the kidney, liver, spleen, central nervous system, eyes and genital tract). The incubation period is around 7 days, this factor depends on the species and the strength of the host immune system however.

The initial immune response will usually remove all Leptospira organisms from the blood and tissues but some will persist in the kidney tubules where they can continue to replicate. The Leptospira organisms in the kidney tubules manage to evade the host immune response by avoiding phagocytosis.

The damage done to the host’s organs and tissues is variable and depends on the virulence of the Leptospira serovar and how susceptible the host immune system is. The most serious of diseases occur in the incidental hosts, i.e. not the primary reservoir host.

Overview of Pathogenesis

Diagnosis

At present there are three different methods of leptospirosis diagnosis:

  • Detect leptospire antigens – Leptospire antigens will induce agglutination of antibodies. This can be tested using a microscopic agglutination test (MAT).
  • Isolation of Leptospires – Leptospires are isolated from the urine or infected tissues. However this can be very labour and time intensive as Leptospira species are slow to culture using growth medium, meaning it can take weeks before a positive/negative result is returned. Despite this, this method of diagnosis is probably the most reliable.
  • Polymerase Chain Reaction (PCR) – Molecular methods of diagnosis (such as PCR) are gaining popularity for diagnosing Leptospirosis, however PCR is unable to distinguish between serovars.

Prevention

For dogs there are currently two forms of vaccine available:

  • In the UK, a bivalent vaccine is used which protects against two serovars – canicola and icterohaemorrhagiae.
  • In the USA however, a quadrivalent vaccine is used, this protects against four serovars – grippotyphosa and pomona as well the canicola and icterohaemorrhagiae which the bivalent vaccine covers.

Some preventative measures are also being taken in cattle to protect against Leptospira borgpetersenii serovar hardjo.

The widespread use of these bivalent vaccines may be responsible for the observed decline in classic canine Leptospirosis infections, however this vaccine does not provide cover for other serovars.

In the USA canine leptospirosis has been classified as a re-emerging disease due to the increasing amounts of newly diagnosed cases. This may be due to the prevalence of grippotyphosa, pomona and bratislava in wild reservoir species which are spreading Leptospira through the domesticated animal population. This is good reasoning behind the introduction of the quadrivalent vaccine as it protects against these serovars (not bratislava, however cases of bratislava are low).

In the UK, rural cases of canine leptospirosis are greater than urban cases, possibly hinting at a greater transmission via wildlife. This is a breakdown of serovar cases diagnosed in the UK:

  • 60% – L. icterohaemorrhagiae
  • 20% – L. canicola
  • 6% – L. icterohaemorrhagiae copenhageni
  • 1.3% – L. bratislava

The Somatosensory System

Introduction

The somatosensory system comprises of ‘senses’ known as sensory modalities, these include; tactition (touch), temperature, proprioception (body position awareness) and nociception (pain). It is possible there are others, and these categories may be broken down further, for example kinaesthesia is the awareness of muscle strain/tension which is a form of nociception/proprioception.

Sensory receptors and sensory (afferent) neurones of the somatosensory system can be found from the periphery (such as the skin, muscles and organs) through to the deeper neurones of the central nervous system. Specific receptors are able to detect different stimuli; the stimulation of a receptor causes information to be sent along neurones to the corresponding area of the brain.

General Organisation of the Somatosensory System

A typical somatosensory pathway will begin with a sensory receptor (for example a mechanoreceptor which is able to detect stress/stretch in the skin – helping to form the tactile sensory modality). The stimulation of the receptor will cause information to be sent to the brain, where it will be perceived (in this example as touch). The information is sent to the brain through the spinal cord, typically three long neurones will facilitate this.

The cell body of the first neurone is located in the dorsal root ganglion of the corresponding spinal nerve. The second neuronal cell body is located in the midbrain for motor/touch sensory modalities and the spinal cord for pain sensory modalities. Neurones involved in pain sensory modalities travel to the thalamus, up the spinal cord via the spinothalamic tract.

It is at this point that the ascending neurones cross-over (decussate) to the opposite side of either the spinal cord or midbrain (depending on the sensory modality – above), typically upon entry of the structure of decussation. The axons of these neurones mainly terminate in the thalamus, but may also terminate in the reticular system or cerebellum of the brain.

In the case of touch and pain, the third neurone has its cell body located in the ventral posterior nucleus of the thalamus. The axon of this final neurone terminates in the postcentral gyrus (sometimes referred to as the somatosensory cortex) of the parietal lobe – where sensory information from different modalities is integrated.

Ascending Somatosensory Pathways

Information from sensory modalities is transmitted to the brain, via the spinal cord. These ascending neurones are able to take multiple pathways to reach their destination. These pathways can be split into three main routes.

Dorsal Column Pathway

The dorsal column pathway:

  • This pathway carries tactile and proprioception sensory modality information. Touch discrimination is owed to this pathway.
  • Sensory information arrives through the dorsal horn and is carried to the dorsal columns (which consist of the Gracile & Cuneate fasciculi)
  • The neurones synapse in the Gracile & Cuneate fasciculi of the medulla, where they decussate
  • The neurones terminate at the thalamus; they travel there along the medial lemniscus. The role of the medial lemniscus is simply to carry the neurones from the Gracile & Cuneate fasciculi of the medulla to the thalamus.

Ventrolateral Pathway

The ventrolateral pathway carries all sensory modalities (except proprioception) but is specifically involved in the propagation of pain. This pathway can be divided into two, as there are two possible tracts which the sensory modalities can take. These are the spinothalamic tract and the spinoreticular tract.

The Spinothalamic Tract

  • Nociceptors (pain receptors) detect a stimulus and neurones carry this to the spinal cord
  • These neurones head directly to the thalamus from the spinal cord, without synapsing elsewhere (via the medial lemniscus)
  • This pathway is associated with nociception such as that from thermal stimuli or from a pinprick

The Spinoreticular Tract

  • Follows the same pathway as the spinothalamic tract except the neurones synapse in the reticular formation of the medulla (primarily associated with the sleep/awake cycle)
  • From the reticular formation the neurones continue to the thalamus
  • This pathway is associated with ‘true pain’

Spinocerebellar Pathway

This pathway is associated with muscle and joint proprioceptors primarily, involving it in postural reflexes. Many neurones which travel via this pathway do not decussate, as is common in the other pathways.

After entering the spinal cord from an appropriate proprioceptor (or kinaesthesia receptor etc.), the neurones synapse in the dorsal horn and then head straight to the cerebellum.

Segmental Organisation

The spinal cord can be divided into sections by which part of the body it serves; cervical (head/ immediate upper body & arms), thoracic (trunk), lumbar (lower back/legs) and sacral (hind). Each of these sections is then made up of 5-12 nerve pairs each serving a smaller sub section of the body/skin; they send sensory information to the brain from their corresponding section.

  • Cervical Nerve Pairs – 8
  • Thoracic Nerve Pairs – 12
  • Lumbar Nerve Pairs – 5
  • Sacral Nerve Pairs – 5

This is significant diagnostically, because the deratomes (small section of skin served by a spinal nerve pair) are served by a specific spinal nerve pair. This means pain deriving from a deratome (or area of skin) if located, can be tracked back to its spinal nerve source.

For example, a human with pain in the skin of the abdomen (Thoracic nerve 12 [Th12]) could point out this pain to a doctor. The pain would be a symptom of possible damage to Th12 and further action could be taken.

Reflexes

Certain sensory modalities such as nociception provide information which needs to be responded to rapidly, using the example of nociception the information received may be that a hot object is causing tissue damage and requires the removal/release of the object quickly. This type of action is usually processed without involvement of the conscious brain and is known as a reflex.

Comparing a conscious response to reflex:

Conscious Response


Reflex Response


Reflexes offer the chance to act quickly by using local processing in the spinal cord – without the need for information to travel to the brain, thus saving time. However there is another type of reflex (sometimes called a long loop, compared to a simple reflex – short loop) called an inter-segmental reflex. This type of reflex looks more like a conscious response, yet the conscious brain is still not involved, so it is deemed a reflex. The processing is done in the brainstem or a separate spinal cord segment, the complete pathway is as follows:

An example of this type of reflex is the ‘Tonic-Neck’ reflex; the reorientation of the head (and thus neck) causes a reflex repositioning of the body and limbs to accommodate the new posture.

Receptors

So we have discussed the transmission of somatosensory signals, but what about their detection? As said earlier, receptors found all over the periphery of the body (e.g. skin, muscle, and organs) detect specific stimuli and transmit the information to the brain, but there are multiple types of receptors available to detect the different stimuli.

Mechanoreceptors

Two key attributes of a mechanoreceptor are the size of its receptive field and the speed at which its fibres adapt. The receptive field is important for discriminating from where a stimulus arises. A small receptive field has better discrimination than a larger one. Typically smooth skin has a small receptive field.

The speed at which fibres adapts concerns how quickly the receptors become desensitised to a stimulus. Rapidly adapting fibres will quickly become desensitised and stop generating action potentials to a stimulus (they may fire action potentials when the stimulus is stopped), whereas slow adapting fibres generally continue to fire action potentials during the length of exposure to the stimulus.

Meissner’s Corpuscle

Found in smooth skin, these mechanoreceptors have a small receptive field and rapidly adapting fibres. They are said to perceive fluttering stimuli.

Pacinian Corpuscle

Found deep within all types of skin, these mechanoreceptors have a large receptive field and rapidly adapting fibres. They are able to perceive vibrations.

Merkel Discs

Found in all types of skin, fairly shallow. These mechanoreceptors have small receptive fields and slow adapting fibres. They are able to perceive pressure.

Ruffini Corpuscle

Found deep within all types of skin, these mechanoreceptors have large receptive fields and slow adapting fibres. They are able to perceive stretching.

Free Nerve Ending

Common receptors for temperature and nociception, they are able to express different types of receptors; mechanical, thermal nociception and polymodal nociception (slow burning pain from chemicals, temperature etc.)

Stimulation of Receptors

The majority of somatosensory receptors are modified ion channels, which when stimulated allow the influx of ions and depolarisation which results in the generation of an action potential and its transduction.

Mechanoreceptors like those listed above; require some sort of mechanical stress e.g. stretching, to stimulate them. This causes the shape of the receptor to distort and opens the ion channel.

Chemoreceptors and thermoreceptors are stimulated by their corresponding stimulus, either directly or by the binding of the (chemical) stimulus to the receptor or a protein linked to the receptor. Again, stimulation leads to depolarisation and action potential generation.

Speed of Signal Transmission

The different receptors propagate their signals along nerve fibres which differ in the speed at which they transmit action potentials. Nerve fibres associated with pain are often much slower than those associated with touch. The different nerve fibres are classified as:

  • Aα – The fastest nerve fibre (72-120ms-1)
  • Aβ – Fast (36-72ms-1)
  • Aδ – Small, slow, myelinated fibres associated with nociception and temperature (4-36ms-1)
  • C – Small, very slow, unmyelinated fibres associated with nociception (0.4-2.0ms-1)

Pain

Pain Perception

Pain is the perception of nociception, until ‘pain’ reaches the cortex it is not pain, but nociception. It is believed that there is a ‘pain gate’ in the dorsal horn, the theory is that by preventing a ‘pain’ stimulus from passing through this gate you can prevent its perception as pain – making it a target for drugs.

Triple Response

The triple response is a phenomenon which occurs after inflammation, it results in pain – caused by irritant chemicals released after physical injury/damage. The chemicals are released onto the skin and free nerve endings. This causes nociception information to be sent to the spinal cord for processing, but the chemicals are also able to spread to other local nerves causing the release of more chemicals and more nociception transduction to the spinal cord. The overall effect is the spreading of inflammation and pain to a larger area than was originally damaged.

The Route of the Somatosensory System through the Brain

Upon reaching the brain, the majority of somatosensory information travels through the thalamus and continues further into the brain. From the thalamus, information head to the sensory cortex. Processing here allows the sensory modalities to be perceived.