Pathogenesis of parasitic infections

Question 1

What is the parasite of chagas disease called and describe briefly the main principles of its life cycle?

Answer 1

• Trypansoma cruzi - protozoa
• Basic life cycle:
• 1. Infected bug and defecates at site
• 2. Parasite or person leads to transmissions by invading cells at wound site
• 3. These transform into amstigotes
• 4. These then mutliple into tryopmatsigotes and enter blood
     Can also enter via ingestion where it will multiply within the intestine

Question 2

State the 3 phases of chagas disease distinguishing the key features between them?

Answer 2

• 1. Acute: Incubation 1-2 wks after bite! Up to months after transfusion, Trypanosomes in blood
• 2. Chronic ‘indeterminate’: Lifelong infection, Generally trypanosomes not detectable but often positive for parasite DNA, Seropositive - presence of detectable levels of a specific marker within the serum, 60-70% who become infected will develop indeterminate chagas disease, Normal ECG and X rays
• 3. ‘Determinate’ Chronic disease: Seropositive, 30-40% of infected will develop chronic 10-30 years after infection, 5-10% develop chronic Chagas immediately after acute disease

Question 3

State the key clinical symptoms found in acute chagas with symptoms duration and diagnosis rate?

Answer 3

• Occurs within 3 weeks
• Generally mild or asymptomatic: Local swelling (Romaña), Nodule or chagoma, Fever, Anorexia, Lymphadenopathy - a disease affecting the lymph nodes.
• 1-2% diagnosed with acute chagas due to mild symptoms which are common with other illnesses
• Symptoms last 8-10 wks

Question 4

What are rare clinical symptoms of acute chagas and who do they primarily affect?

Answer 4

• Primarily affect young and immunosuppressed individuals
• Can lead to:
• Hepatopsplenomegaly
• Acute myocarditis
• Meningoencephalitis
• Fatality <5% of symptomatic

Question 5

What are the main organs affected by chronic chagas disease?

Answer 5

Heart and intestinal tract

Question 6

Describe the cardiac impact from chronic chagas?

Answer 6

1. Arrhythmia can occur: Protozoa invades ANS conduction fibres, Damages conduction system of heart via inflammation and fibrosis
2. Thinning of heart muscle: Damage to heart muscle, Heart muscle becomes tinner + distended due to cardiomyopathy -> Enlarged heart, Insufficiency of heart valves - Aneurysm of apex of left ventricle
3. Can lead to heart failure

Question 7

Describe the digestive impact from chronic chagas?

Answer 7

• Develops in 10-15% of patients with chronic infections
• Esophagus, rectum, and sigmoid colon most affected
• Ineffective peristalsis occus due to loss of ANS - accumulation of faeces

Question 8

What frequent clinical symptoms arises from chronic chagas and state the complications of it?

Answer 8

Megacolon - Presentation: Constipation
• Complications: Faecaloma, Obstruction, Sigmoid volvulus! Ulceration, Perforation

Question 9

State the acute chagas pathogenesis

Answer 9

• Tissue damage caused by inflammatory response to parasite in nests of amastigotes in cardiac, skeletal, and smooth muscle
• Parasite killing by antibodies, activated innate immune response and Th1 pro- inflammatory cytokines.

Question 10

State the pathogenesis of indeterminate chronic chagas disease

Answer 10

Regulatory immune response characterized by IL-10 and IL-17

Question 11

State the pathogenesis of chronic chagas disease

Answer 11

• Chronic inflammatory response to persistent parasites in muscle and nerve cells
• Autoimmune mechanisms
• May vary by parasite strain and tissue tropism
• Predominance of Th1 cytokines and CD8+ T cells

Question 12

State the 3 main species of schistosomiasis?

Answer 12

• Schistosoma mansoni
• S.haematobium
• S.japonicum

Question 13

Describe the life cycle of schistosomiasis?

Answer 13

VD

Question 14

What dermal disorder can arise from schistosomiasis and how?

Answer 14

• Cercarial dermatitis - exposure to cercariae from animal or bird schistosomes - Causes rash-like lesions
• Requires pre-sensitization
• Allergic-type reaction

Question 15

What is the key feature of the immune response against schistosomiasis and what can it result in?

Answer 15

• Granuloma formation
• Originally eggs live in the venous system, but backflow can occur causing eggs to move into the liver.
• Here eggs can become organised in granulomas - leads to inflammation and damage to tissue - Followed by repair and fibrosis
• Overtime Repeated insults and tissue repair leads to fibrosis and organ damage to liver
• Extra info: The eggs formed in the mesentery are pushed through the capillaries, through the intestinal and mucosa and are then excreted.

Question 16

How can hepato-intestinal schistomsomiasis arise?

Answer 16

• Infections with S.mansoni and S. japonicum
• Pathology caused by immune response to eggs (granulosa formation)
• Typically leads to liver damage

Question 17

What is the first clinical sign of urinary schistosomiasis?

Answer 17

Haematuria - Presence of blood within the urine

Question 18

Describe the bladder pathology from Urinary schistosomiasis?

Answer 18

Repeated episodes of US within the bladder will cause inflammation eventually causing neoplastic chances to occur with the bladder mucosa - Carcinoma can occur

Question 19

Describe onchocerciasis, what it is caused by, its vector and how its transmitted?

Answer 19

• Major blinding disease
• Caused by filarial parasite (Onchocercavolvulus)
• Transmitted by blackflies
• Vector: Simulim

Question 20

Describe the life cycle of Onchocerciasis?

Answer 20

• bites + invades through the skin

Question 21

Describe the pathology of Onschocerciasis?

Answer 21

• Repeated episodes of inflammation to presence of microfilariae (the minute larva of a filaria) leads to permanent damage and scarring in skin and eyes

Question 22

Describe the clinical symptoms of the Onchocerciasis?

Answer 22

• Onchocercal nodules
• Skin disease
• Eye disease

Question 23

State 3 examples of skin disease that can arise from
Onchocerciasis?

Answer 23

• Acute papular onchodermatitis
• Chronic onchodermatitis
• Sowda

Question 24

State examples of anterior and posterior segment eye diseases from Onchocerciasis?

Answer 24

• Anterior segment: Punctate keratitis! Acute iridocyclitis! Sclerosing keratitis
• Posterior segment: Optic neuritis/atrophy, Chorioretinopathy

Question 25

Describe the immunopathogenesis of onchocerciasis?

Answer 25

- Acute will actively forms antibodies against it - Overtime suppression of immune response against infection due to continious infection-> regulatory environment - AAM = Alternatively activated macrophages

Question 26

Explain the immunopathogenesis of onchocerciasis?

Answer 26

- Initially primary response will be a strong immune response, but with repeated infections the immune response is also causing pathology - So immune system has to switch off when infection occurs otherwise it will kill you

Question 27

What are ticks?

Answer 27

- Ectoparasites which cause tick bites in your skin and release a toxin into the skin which blocks motor fibres - Can cause mechanical injury at site - Tick paralysis can occur if tick not removed from site due to toxin long term

Question 28

State the two types of ticks and what they can transmit?

Answer 28

- Hard ticks: transmit are typhus, encephalitis, fevers, tick paralysis (rapid onset of muscular paralysis due to failure of ACh liberation from NMJ), tularaemia and human babesiosis. - Soft ticks: transmit Q fever and relapsing fever.

Question 29

What disease does ticks normally cause?

Answer 29

Lyme disease

Question 30

Describe head lice?

Answer 30

- Head lice - Suck blood from scalp & lay eggs on hair - Common & easily spread by close contact, sharing of combs, brushes, hats etc

Question 31

Describe body lice?

Answer 31

- Body lice - Suck blood from body & lay eggs on clothing - Uncommon & spread by bodily contact, sharing of clothing or bedding - Vector diseases (epidemic typhus, trench fever, relapsing fever)

Question 32

How can lice be transmitted or be affected?

Answer 32

- Lousiness related to sanitation - Crowded conditions - Long periods without bathing or changing clothes

Question 33

Describe the pthiridae lice, where its found and how it spreads?

Answer 33

- 2 important families (attack humans) - Pthiridae (crab lice, public lice): - Broad, flat lice that appear crablike - Mid & hind legs are stout with very large claws - Abdominal segments have distinct lateral lobes - Single species (Pthirus pubus) confined to human pubic region • Bites cause irritation & typical rash Spread by close body contact (usually sex) • No diseases

Question 34

What is the alternative name for botfly known as and describe how they work?

Answer 34

- Dermatobia hominis - Botflies are parasitic organisms and some lay their eggs in mammals. Like human mammals. One type of botfly latches onto mosquitoes mid-flight, attaching their eggs to the mosquitoes' stomachs. Then, when a mosquito lands on a human's skin, the eggs burrow into the tiny wound left by the mosquito bite - Eventually, these eggs turn into larvae and will dig their way out from underneath the skin

Question 35

State drugs used to control protozoa infections?

Answer 35

- Tinidazole - Metronidazole - Nitazoxanide - Benznidazole - Heavy metals (meglumine antimoniate)

Question 36

State drugs used to control helminths infections?

Answer 36

- Albendazole/ mebendazole - Praziquantel - Ivermectin - Diethylcarbamazine - Pyrantel

Question 37

State drugs used to control ectoparasites infections?

Answer 37

- Ivermectin - Benzyl malathion lotions

Question 38

Describe 3 forms of control of parasitic infections without drugs?

Answer 38

Behaviour, environmental interventions, poverty reduction

Question 39

In terms of behaviour, how can we control parasite infections?

Answer 39

- Education - Hand washing and hygiene behaviours

Question 40

In terms of environmental interventions, how can we control parasite infections?

Answer 40

- Spraying of residual insecticides for household vectors - Mosquito nets for malaria - Improved housing - Sewage disposal and potable water - Drainage of swamps

Question 41

In terms of poverty reductions, how can we control parasite infections?

Answer 41

Micro-financing, etc

Question 42

Treatment of parasite infections Describe the frequency and duration of treatment given areas with parasite infections (PART 1)

Answer 42

- For many parasite infections in an endemic settings, treatment must be given periodically over long periods of time because re-infections are rapid or because the treatment kills larval rather than adult stages - A single dose of albendazole is given to high risk groups such as schoolchildren up to every 4 months to control STH infections.

Question 43

Treatment of parasite infections Describe the frequency and duration of treatment given areas with parasite infections (PART 2)

Answer 43

- A single dose of ivermectin is given to endemic communities (mass drug administration) every 6 or 12 months to control onchocerciasis - A single dose of praziquantel is given to endemic communities (mass drug administration) every 6 or 12 months to control schistosomiasis