African trypanosomiasis Flashcards

1
Q

What species cause HAT?

A

Trypanosoma brucei - broad species
Sub species
West african - caused by T.b gambiense
East african - caused by T.b rhodesiense

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2
Q

What is the vector for african trypanosomiasis?

A

Tsteste fly - glossina mortisans
painful bite
Identified by hatchet cell
Trypanosomiasis only in sub saharan africa

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3
Q

How do east and west african trypanosomiasis differ?

A

caused by different species, rhodesiense vs gambiense

location, east vs west africa

reservoir, animals - wild game, cattle vs humans - domesticated pigs

progression - weeks to months vs months to years

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4
Q

Pathophysiology of trypanosomiasis

A

Tsetse fly bites its host, thereby injecting metacyclic trypomastigotes into the skin

Trypomastigotes then transform into bloodstream trypomastigotes, allowing them to travel throughout the body where they multiply by binary fission

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5
Q

What does antigenic shift cause?

A

Antigenic shift - near continuous modulation of variacble surface glycoproteins, which allows the parasite to rapidly switch expression of surface proteins to constantly evade host immune repsonses.

as a result there are typical waves of parasitemia that occur with each antigenic shift and then subside as immune system begins to develop a response.

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6
Q

What is stage 1 and the clinical presentation?

A

1-3 weeks after bite, trypanosome parasites spread through blood stream and lymph nodes - stage 1, early haemoplymphatic stage - trypmastigotes can be seen on blood smear

  • slow progression - WA
  • rapid progression - EA
  • fevers
  • headaches
  • malaise - feeling unwell and tired
  • Arthralgia - joint pain
  • waves of fever
  • chancre at bite site

other non specific symptoms
- pruritus
- rash
- weight loss
- facial swelling

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7
Q

What is the immune response?

A

Symptoms may subside as non-specific polyclonal B cell activation with large production of IgM and resultant enlargement of the spleen and lymph nodes

Diffuse lymphadenopathy, hepatomegaly and more commonly, splenomegaly are often present

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8
Q

What is the clinical presentation of stage 2 - late/encephalitic/CNS phase?

A

Trypomastigotes can easily pass into the CSF
Onset in weeks – EA
Months – WA
Diagnosed by WCC in CSF

CNS related symptoms
- Headaches, poor concentration
- Difficulty completing tasks
- Psychosis, personality change
- Tremor, ataxia

Hallmarks of late disease is alteration in the normal circadian rhythm, with reversal of the sleep-wake cycle, hence name sleeping sickness

Convulsions may occur as the disease progresses, especially in children, though meningismus and focal neurologic signs are often absent

Clinical deterioration until coma or stupor results

Stage II disease is universally fatal without treatment

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9
Q

What can you look for when diagnosing?

A

Non specific abnormalities

Anaemia, leukocytosis and throbocytopenia, likely due to splenic sequestration

Hypergammaglobulinemia with polyclonal IgM is characteristic

Other common findings include elevated ESR/CRP and hypoalbuminemia

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10
Q

How to diagnose HAT with microscopy?

A

Definitive diagnose requires detection of parasite in blood, CSF, or lymph node aspirate

Testing the buffy coat increases sensitivity

Giemsa stain

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11
Q

How to diagnose HAT with serology?

A

Antibody testing is available for T.b gambiense but is not sufficient for definitive diagnosis as you can get false positives or cross reactions with other types of trypanosomes. There is neither antigen or antibody testing for T.b rhodesiense

Most frequently used detection method is the card agglutination test for T.b gambiense (CATT), relies on the agglutination of trypanosomes and antibodies and has a sensitivity of 94-98%

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12
Q

What are morula cells?

A

Engorged plasma cells, rare to see but can be used to diagnose trypanosome.

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13
Q

Treatment of T.b gambiense and rhodesiense stage 1 and 2

A

Gambiense:
stage 1 - pentamidine, fexinidazole
stage 2- nifurtimox plus elfornithine (NECT)

rhodesiense:
stage 1: suramin
stage 2: melarosprol

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14
Q

Drugs for west african tryps

A

Pentamidine – hypotension, electrolyte disturbances

Nifurtimox – GI upset

Eflornithine – dizziness, headaches, nausea

Fexinidazole – neuropsychiatric, QT prolongation

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15
Q

drugs for east african try[s

A

Suramin – nephrotoxicity, myelosuppression and peripheral neuropathy have been reported

Melarsoprol – arsenic derivative, used for late CNS stage of EA tryps. Common side effects include irritation at the injection site, abdominal pain, vomiting, diarrhoea, myocarditis and peripheral neuropathy

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16
Q

How to control tryps?

A
  • active case finding
  • treatment
  • reservoir control (Cattle)
  • vector control (tsetse)
17
Q

How can you prevent tryps?

A
  • No vaccine
  • Prophylaxis not feasible
  • Avoid blue colour – attracted to blue
  • Thick clothing, they bite through light calls, can get through thick clothes as they’re made to bite cattle
  • DEET works but not well
  • Day biters so bed nets don’t help
18
Q

Eflornithine - WA

A

Developed as an antineoplastic in early 1980s by chance it was found to have active anti-tryp activity

Safer than melarsoprol

Effective in stage 2 gambiense (WA) but not rhodesiense (EA) disease

Not widely available

Resource heavy regimen of 14 days QDS infusions,

Not active against rhodesiense

19
Q

NECT RCT

A

Nifurtimox-elfornithine combination therapy for second stage african trypanosoma gambiense, did a randomised trial

NECT combination therapy is non inferior – just as good and less toxic

Less toxic than 14 days eflornithine

Easier and cheaper to administer

Has to be non-worse or just as good

As a result NEXT added to WHO essential medicines list as treatment against sleeping sickness