Life-cycle of Trypanosoma gambiense

 



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Life cycle of        Trypanosoma gambiense 



Describe the structure and life history of Trypanosoma gambiense. What diseases does it cause? Describe transmission and pathogenesis. Discuss the treatment and prevention of this disease.





Trypanosoma gambiense causes the dreaded disease of African sleeping sickness or Gambian trypanosomiasis in humans.


In the early stages, the parasite lives in blood bloodstream and lymph glands of the infected person.

Later it invades the cerebrospinal fluid of the central nervous system leading to symptoms such as fever, anaemia, lethargy and ultimately death.


Chief vector: Tsetse fly ( Glossina palpalis )


Note* G. tachinoidese is also an important known transmitter.


Temporary or reservoir hosts :

Occasionally the trypanosome utilises domestic and wild mammals such as monkeys, dogs, pigs, antelopes, buffaloes and reedbucks as temporary hosts.


These animals do not continue the development cycle but serve as waiting points for the parasite's transmission to humans via the tsetse fly bite 




Morphology of Trypanosoma gambiense :



Structure of Trypanosoma gambiense under light and electron microscope (diagrammatic)
Diagram of Structure of Trypanosoma gambiense
 ( under light and electron microscope )


Shape and size :

The organism is unicellular, and microscopic and exhibits a leaf-like, elongated, flattened shape. The anterior end where the free flagellum is located, is pointed, while the posterior end is blunt.


Size: length - 10-40          micrometers

          width - 2.5-10 micrometers 


Developmental forms :

T. gambiense is polymorphic,  presenting two developmental forms.

  •   Trypanosome form 
  •   Crithidial form


1. Trypanosome form :

In a vertebrate host ( humans ), It can appear, 

  • long Slender or 
  • short stumpy or 
  • intermediate forms.


In invertebrate host ( Tsetse fly ),

  • In midgut - it is long and slender.
  • In salivary glands - It is short and stumpy.


2. Crithidial form  :

Only found in the salivary glands of tsetsy flies.



Pellicle  : 

The entire body of the trypanosome is externally covered by a thin elastic covering called a Pellicle, which is supported by fine fibrils known as microtubules aiding in maintaining the shape of the organism while it swims in blood plasma.


Flagellum :

A Single flagellum originates from the basal body ( kinetisome ) near the posterior end of the body. Extending forward along the entire length of the body and free at the anterior end.


In T.S., under the electron microscope,  the flagellum exhibits a typical 9 + 2 arrangement of internal fibril and features unilateral hair.

Function :

In blood,  when the trypanosome moves, the undulating waves pass from the tip to the base of the flagellum. It has an important role in motility, cellular morphogenesis, cell division, immune response and potentially sensory perception.

 

Undulating membrane :

The beating of the flagellum causes the pellicle to form membranous folds known as the undulating membrane 

Function: It is believed to enhance locomotion in the viscous environment of blood.


Note*: This is believed to be an adaptation for locomotion in the viscous fluid  ( blood ).



Cytoplasm

The cytoplasm is enclosed within the pellicle. In the cytoplasm which is differentiated into ectoplasm and endoplasm, there are,

Basal body or blepharoplast :

Electron microscopy reveals the presence of a reservoir at the posterior end, with the basal body or blepharoplast of the flagellum located at its base.


Mitochondria

An elongated and uneven mitochondria with tubular cristae is present in the cytoplasm extending from one end of the body to the other.

Near the blepharoplast, the mitochondrion forms a disk-like structure known as the parabasal body or kinetoplast, which contains a double-stranded DNA helix which lies anteroposteriorly within the disc.


Golgi apparatus

 It is present in between the reservoir and the nucleus.


Endoplasmic reticulum

Is present throughout the cytoplasm.


Ribosomes

Ribosomes are found both on the endoplasmic reticulum and freely scattered in the cytoplasm.


 Volutin granules  :

There are numerous greenish refractile granules present in the cytoplasm, which are supposed to store food particles chiefly glycogen and phosphates.


Vacuoles :

Small vacuoles are also seen in the cytoplasm containing hydrolytic enzymes ( lysosomes ).


Nucleus

The organism possesses a large, oval and vesicular nucleus characterised by double-unit nuclear membrane-bearing pores.


The nucleolus or endosome is centrally placed with chromosomes scattered within the nucleoplasm.



Life cycle of Trypanosoma gambiense :


T. gambiense exhibits a digenetic life cycle, completing its development in two hosts.


The primary principal or definitive host is a man and the intermediate host or vector is a blood-sucking insect called Tsetse fly ( Glossina palpalis ).


Other mammals like antelopes, pigs, buffaloes etc also act as reservoir hosts harbouring the parasite.


Diagram depicting the stages of life cycle in human and tsetse fly
Diagram of Trypanosoma gambiense life-cycle



Life cycle in humans :

All the stages of parasites in humans are extracellular as they are present in the blood plasma and not inside blood cells


Infection :

The first step to infection in humans is by the bite of the Tsetse fly ( Glossina palpalis ). 

This tsetse fly has infective metacyclic forms in the lumen of its salivary glands which is released in the bloodstream of the human while feeding. 

The fly's saliva contains anticoagulants that prevent blood clotting allowing the trypanosome to enter.



Multiplication :

In human blood, the metacyclic forms which are devoid of flagellum get transformed into long Slender forms with flagella.


These parasites now swim freely by beating their flagella and by vibrating their undulating membrane.

They start multiplying by longitudinal binary fission for which they obtain energy by anaerobic glycolysis.


Metamorphosis

The multiplication of Trypanosomes ceases with the production of antibodies in blood which hampers the process of glycolysis and glucose absorption.

Trypanosomes now shrink to short stumpy forms devoid of free flagellum

During this transformation, the intermediate forms with a somewhat shortened body and a small free flagellum also appear. The energy supply is by the aerobic oxidation of pyruvic acid.


These stumpy forms do not feed and ultimately die unless ingested by a tsetse fly along with the blood meal.


Relapse of infection :

In some cases, long and slender trypanosomes do not transform, but change the antigens of blood to which the host has produced antibodies resulting in survival of the Slender forms which multiply in blood and lead to future relapse of the infection.


Life cycle in Tsetse fly :


Transfer to Tsetse fly :

When the Tsetse fly feeds on an infected person, it ingests short stumpy forms of the trypanosomes which develop further in the vector.


Development in mid-gut :

Further development proceeds in the insect's mid-gut within the peritrophic membrane where they transform into long Slender forms and multiply by longitudinal binary fission. 

The kinetoplast moves farther from the posterior end of the body.

Here the energy yielding process is related to the mitochondrial oxidation of pyruvic acid.


Development in salivary glands :

The long Slender forms make their way into salivary glands via the oesophagus and mouth parts of the insect. They now metamorphose  into crithidial forms characterised by,

  • short body
  • reduced free flagellum and  
  • kinetoplast in front of the nucleus.

Also, the mitochondrion shows the development of an extensive network of cristae enabling the parasite to respire more economically as the blood glucose level falls.

These crithidial forms of trypanosomes multiply in the lumen of salivary glands and transform into Slender metacyclic forms. Now the mitochondrial activity is again suppressed.

This tsetse flies when bites a healthy person, it transfers the metacyclic forms along with the saliva into his blood where it initiates a new infection.



African Sleeping sickness (Gambian trypanosomiasis) :

T. gambiense causes the disease of West African Sleeping sickness or Gambian trypanosomiasis in humans.


Symptoms and pathogenesis :

The initial bite of tsetse fly results in local irritation which subsides after a few days. Infection is caused by the introduction of trypanosomes into the human bloodstream. There they develop and invade the lymphatic glands causing their swelling.


The progression of the disease occurs when the parasite invades Cerebrospinal fluid of the central nervous system.


Symptoms :

1. Irregular recurrent fever.

2. Generalised weakness.

3. Loss of weight.

4. Anaemia.

5. Increase in pulse rate.

6. Severe headache.


Further progression of the disease, the patient shows episodes of sleepiness, first at regular intervals and then leads to a state of coma. The ultimate fate is death.


Diagnosis :

Patients blood samples are microscopically examined. Also, samples of chancre fluid, lymph node aspirates and bone marrow can be examined.


Treatment :

After laboratory blood tests and confirmed diagnosis, the standard treatment for first-stage ( haemo lymphatic ) disease is,

Pentamidine and for second-stage disease Melarsoprol is used.


Prevention :

Prevention of the disease of trypanosomiasis depends upon the eradication of the vector, i.e. the tsetse fly.
  • Clearing out bushes,
  • Spraying of DDT,
  • Nets may be used to prevent tsetsy flies and
  • Breeding grounds of tsetsy fly should be destroyed.




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