Question 3.

Discuss: “As with other infectious agents, the clinical manifestations of parasitic disease may reflect tissue damage by the parasite, the effects of the host immune system, or both.”

Cienne Morton

Parasites invade and damage their host, who retaliates by releasing a barrage of harmful factors upon the parasite or parasite-infected cells. The symptoms of infectious disease reflect these hostile exchanges between host and parasite. Clinical manifestations of the disease can be a result of parasite-mediated tissue damage (e.g. due to toxin release or cell lysis), nonspecific damage caused by the immune system (the immune system killing the body’s own cells), or not really damaging at all, but inconvenient characteristics of a heightened immune response (like a runny nose and minor headache).


Parasite-mediated damage

• Microbial damage to the host is usually in the form of toxins or other factors that degrade cells. The effect of bacterial toxins is seen in the clinical presentation of botulism, tetanus, bacterial dysentery, anthrax and cholera. The clinical presentation of parasitic diseases is similarly dictated by parasitic destruction of host tissue. Examples are given below:
  
  Plasmodium (protozoan - malaria)
  o Causes erythrocytes to display ‘sticky’ protein on cell surface, making them adhere to vessel walls. This can block some vessels and lead to lack of perfusion to blood brain barrier, leading to coma
  o Haemolysis by the parasite causes anaemia and haemoglobinuria
  
  
  Naegleria (protozoan - amoeboid meningoencephalitis)
  o attacks brain tissue: primary amoebic meningoencephalitis
  o ‘eats’ brain tissue through trogocytosis (uptake of plasma membrane constituents) and release of cytolytic molecules and protein-degrading enzymes
  o Confusion
  o Loss of balance, seizures, hallucination
  o Altered sense of taste, smell
  o Serious, less than 1% survival in later stages
  
  Leishmania (protozoan - leishmaniasis)
  o Cutaneous: skin lesions
  o Visceral (infects liver, spleen) – most serious, near 100% mortality if untreated
  
  Trypanosoma brucei (protozoan - African sleeping sickness)
  o Crosses blood brain barrier, infects brain
  o neurological disturbances: diurnal somnolence and nocturnal insomnia
  o extrapyramidal (tremor, motor incoordination)
  
  Ascariasis (helminth)
  o Nutrional deficiency (worm feeds on food from host in intestines)
  

Immune system-mediated symptoms

• The clinical presentation of a disease is hardly ever due to parasitic tissue damage alone. Whenever a pathogen attacks a host, an immune response will be triggered. Infection by a microbe triggers inflammation, the protective response of the host. Many symptoms common to different infections are due to inflammation, triggered by the pathogen but facilitated by the body’s own immune system, such as a runny nose, coughing and sneezing. The immune response plays an important role in influencing the clinical presentation of parasitic diseases. Examples of immune-mediated symptoms are:
  
  redness, swelling, pain, pus at site of skin infection
  o chancre in some cases of trypanosomiasis at site of fly bite
  
  rash
  o trypanosomiasis
  
  lymphadenopathy
  o Winterbottom’s sign in trypanosomiasis
  
  hepatomegaly, splenomegaly are signs of immune upregulation
  o trypanosomiasis
  o malaria
  o schistosomiasis
  o leishmaniasis
  
  While damage may be caused by an invading parasite, the sensation of pain is caused by the body. Symptoms such as headache and abdominal pain are due to the body while signs like damage are due to the parasite.
  o Headache in malaria, naegleria infection, trypanosomiasis
  o Abdominal pain: schistosomiasis (helminthic)
  
  Fever: caused by pyrogenic factors that are released by the nervous system in response to infection and is present in a multitude of infectious diseases.
  o Malaria
  o Trypanosomiasis
  o Leishmaniasis
  o Naegleria
  o Schistosomiasis
  
  Diarrhoea: can be pathogenic, triggered by invading pathogen or substance, or can be mediated by the host in a bid to expel gastrointestinal parasites. Present in schistosomiasis
  
  Anaemia:
  o Journals have recently reported that haemolysis by Plasmodium may only account for 10% of the red blood cell destruction associated with malaria. 90% of the destruction may actually be due to phagocytes ingesting non-infected red blood cells.
  
  The immune-mediated symptoms above are designed to protect the host, but on occasion the immune system may inadvertently potentiate the disease. African Sleeping sickness (trypanosomiasis) is characterised by an early (haemolymphatic) and late (meningoencephalitic stage). In the latter stage, the trypanosomes have traversed the blood brain barrier and interfere with neurological function. The mechanism by which the protozoa penetrate the blood brain barrier is not fully characterised, but it has been reported that the immune response may play a part. Upon inflammation, the immune system releases inflammatory cytokines that increase the permeability of blood vessels (like prostaglandins, TNF-alpha, IFN-gamma), so that when brain-associated capillaries become inflamed, the normally impermeable endothelium becomes permeabilised. In this case, the immune system aids the progression of trypanosomiasis, and may actually facilitate the neurological stage of the disease.

In parasitic diseases discussed here, both parasite-mediated damage and the host immune response influence the clinical presentation of a disease.