Trypanosomiasis, Leishmaniasis Flashcards
The main source of oral Chagas
Acai fruit
Also cane sugar juice
Congenital chagas when rx?
Dont treat during pregnancy as teratohgenic risk
Aim to detect congenital early.
Then treat mother and child (Benznidazole or nifurtimox)
chagas in breast milk?
Only in acute infection
NOT chronic form
Contraindications to chagas rx
Pregnancy
CKD
End stage cardiac disease
Old and historic exposure only
What does rx for chagas not prevent
Poor cardiac outcomes in those with established Chagas cardiac disease
What causes sleeping sickness?
All found in Africa but which type confined to domestic and wild animals?
Which is west / central Africa?
Which in East and southern?
Which is worse with more rapid progression?
- Trypanosomiasis
- T brucie bruicie in animals only
- T brucie gambiense in West/central
- T brucie rhodesiense in East/South - worse with more rapid progression of sx
African Trypanosomiasis Vector? ? Lifecycle
- Tetse fly (genus Glossina)
- Trypomastigotes taken up by tetse and multiply by fission in stomach then penetrate gut wall and move to salivary glands . Fly takes about 20 days to become infective and remains infective for rest of life
African Trypanosomiasis local sx?
- Chancre appears around 3 days after bite and increases in size for 3 weeks
- May get lymphadenopathy
Acute African Trypanosomiasis systemic effects? After how long?
Parasitaemia after 5-12 days. Gets fever in waves due to antigenic variation (Variable Surface Glycoproteins,)
-> incomplete immune response.
Later, they enter CNS to cause a lymphocytic meningoencephalitis
Why do you get waves of parasataemia in African Trypanosomiasis?
Main response is IgM production which partially controls parasataemia but parasites have antigenic variability which means immune control is incomplete
What is kerandels sign?
- Delayed hyperaethesia in Trypanosomiasis
- Apply firm pressure over a bone -> delay before patient shows signs of pain
Compare Trypanosoma brucei gambiense and Trypanosoma brucei rhodesiense
Trypanosoma brucei gambiense
- Fever, headache, joint pains, lymph glands enlarged in Posterior neck. Generalised pruritus
- Characteristic thickening of facial tissue -> sad or expressionless face. Mild splenomegaly
Late stage -> Behavioural / psych disturbance. Sleep wake pattern reversed qand slowly starts to sleep all of the time. Progress to general CNS / Cerebellar signs
Death usually in months of CNS involvement
Trypanosoma brucei rhodesiense
- Prominent fever and systemic sx
- Pleural/Pericardial effusions common with myocarditis
- May cause jaundice and anaemia
- Lymph enlargement in groin / axillary
- Death usually within a few weeks and before prominent CNS signs due to myocarditis
African Trypanosomiasis dx?
- Thick blood films (can use romanowsky stain like in malaria)
- [Note may be difficult to find especially in late stage t b gambiense]
- Posterior cervical lymph gland aspirate in T.b. gambinese
- Bone marrow aspirate- often used if negative in early stages
- Aspirate the chancre
All patients with African Trypanosomiasis should have LP. What needs to happen before this? What stain for LP? Seen?
- 2 doses of either suramin or pentamidine to reduce risk of introducing parasites into CSF
- Romanowsky stain
- Very high CSF IgM
- Increased protein or sometimes trypomastigotes
Screening test for African Trypanosomiasis? What do you do before starting Rx?
- Card indirect agglutination test for trypanosomes (CAITT)
- Can use just CATT for t.b. gambinese
- Lateral flow other option
Need to confirm parasitology before starting rx
-Blood smear (thick thin drop)
-Lymph node aspiration
-Blood concentration methods
[Card African Typano - CAT test]
Rx of African Trypanosomiasis
West african?
East / south African?
West African - T b gambiense
Fexinidazole for both stages
[OR
-Early disease - pentamidine
-CNS - NECT nifurtimox, eflornithine combo tx ]
East African - T b rhodesiense
-Early - Sumarin
-CNS - Melarsoprol + surmarin + prednisolone
[West Games Play Evenly
East Rather Sneaky Managing]
What combination of drugs often used in Late stage t.b. gambiense infection (with CNS features)
Eflornithine and Nifurtimox
Which African Trypanosomiasis makes up 90% of infections
- T b gambiense
T b gambiense vs rhodesiense usual hosts
- Gambiense hosts usually human and may see linear patterns of infections along river
- Rhodesiense often hosts in cattle / antelope
Sleeping sickness control
- Detection and treatment of cases. Using CATT or CIATT or blood / gland screening where cases present.
- Need to establish effective treatment centres when an outbreak
Vector control - May need to treat cattle in epidemic
- Insecticide-treated traps
South American Trypanosomiasis also called? Caused by? Key difference in appearance to t brucei?
- Chagas disease
- Trypanosoma cruzi - has large kinetoplast
South American Trypanosomiasis Vector? key ways you get infected?
- Triatomine bugs (all stages feed on blood but only adults can fly)
-triatoma infestans
-or Rhodnius prolixus
-Panstrongylus,
Trypanosomes are excreted in bug faeces - may rub into wound or conjunctiva
-Bite from triatoma infestans
-or consume if on food
-Blood (especially platelet transfusion)
Acute vs chronic chagas sx? How many people get chronic
Acute - Oedema at site of entry either bite or orbital oedema (romanas sign)
- Then lymphadenopathy, hepato/splenomegaly
15-40% get chronic
- Biventricular cardiomyopathy, megaoesophagus/megacolon
[Big oedema at site of infection followed by big liver and spleen followed by big oesophagus and colon]
What causes megaoesophagus and megacolon in chagas
Damage to parasympathetic nerve plexus
Chagas dx
Ideally PCR / ELISA
Blood microscopy in resource limited
[Xenodiagnosis (take an uninfected bug and allow to feed on pt. Then after 3 weeks dissect bug and look for the parasite in gut)]
Name a drug rx of acute chagas
Benznidazole for 2 months
[Or Nifurtimox]
Chagas reservoir? Name 2 control methods of chagas ?
- ONLY mamals infected - Rodents or small marsupials are most common reservoir
[Think about mice in labs] - Blood transfusion screening
- Spraying of Insecticide - Piretroids
- Elimination of cracks in walls/replacement of rooves with metal sheets reduces habitat of bugs
Presents with fever, Posterior cervical lympadenitis with an expressionless face?
T gambiense
Trypomastigote: blood form
Found in the blood of infected mammals
What disease might I give you?
Chagas - Triatoma infestans
Trypomastigote
Nucleus in centre, kinetoplast at head
EPIMASTIGOTE
Amastigote in chagas
Amastigotes chagas
Chagas life cycle
T cruzi vs T brucie
What stage for replication in humans?
Where in vector is it found?
Testse fly for west Africa? east African?
West - Gambinese - Glossina palpalis
East - Rhodesiense - Glossina morsitans
[The MORtality is higher with Rhodesiense]
African Trypanosomiasis life cycle
Infective vs diagnostic stage?
Infective - Trypomastigotes
Diagnostic - Trypomastigotes
Which leish vector in new world? Old world?
Lutzomyia sp. in the New World
Phlebotomus sp. in the Old World.
[Plebs in life of brian = old]
Leish life cycle
The infected person bitten by sandfly
Takes up macrophages infected with amastigotes
Amastigotes tun into promastigotes in gut which divide
Sanfly takes blood meal and inject promastigote
Taken up by macrophages and turn into amastigotes
amastigotes break out of cell
Main cause of cutaneous leish in old world
L. L. Major
Which specific leish in Ethiopia
L L aethiopia
Can you distinguish amistagotes of leish on microscope?
no morphologically the same
Leissh new world which causes visceral disease?
Leishmania infantum (syn. L. chagasi).
Which leish key one causing cutaneous and mucocutaneous disease
L V Braziliensis
Distribution of L V braziliensis?
peru, bolivia, brazil, paragua
Cutaneous leish incubation?
2-8 weeks (max 3 yrs)
Localised cutaneous Leishmaniasis appearance? Rules to be classed as localised cutaneous?
pink-coloured papule that enlarges and develops into a nodule or plaque with a raised border
Max 10 lesions, no more than 2 body areas
Cutaneous leish
Cutaneous leish which is painful usually means?
Bacterial superinfection
What am I? (Not sporotricosis)
Cutaneous Leish sporotrichoid - nodular
Some nodules - Note more than 10 lesions along lymphatic
What am I
severe lymphatic leish
What needs to happen if leish looks like this?
Biopsy verrucous leish - can;t diagnoses clinically
Which Leishmaniasis species if on face with surrounding satellites
L peruviana
Big differentials with cutaneous leish
Buruli
cutaneous tb
sporotricosis
leprosy
Disseminated cutaneous leish need to have
> 10 lesions and >2 body areas
usually lots of different stages of lesion Eg some ulcerated
Difference in appearance of diffuse leish to cutaneous ? Which leish specifically ?
Dont ulcerate;
rather, amastigotes spread to macrophages in other areas of the skin
Usually L V braziliensis
Cause of mucosal leish? Key issue?
Viannia subgenus, especially L.V. braziliensis
[ L.V. guyanensis]
Destruction of nasal cartilage
Disseminated vs diffuse leish more likely vs less likely to have positive skin test?
Disseminated - positive test
Diffuse cutaneous - Negative (due to poor immune response) (LOADS of amastigotes on biopsy)
- can’t contain infection as cant form ulcers
What am I? Key DDx
Mucosal leish
Paraccoccidiodomicosis - often with respiratory Sx / loss of teeth
Diagnosis of cutaneous and mucosal leish
Direct Smear (Scrapping)
◦ Culture
◦ PCR assay
◦ Biopsy: Histopathology
Immunological test
◦ Leishmanin Skin test - poor sens and spec
What is this? which stain?
Giemsa stain
Amastigotes (leish)
Method to get sample for leish from ulcer?
Clean first, then take sample from border
Loads of amastigotes there (spot a kinetoplast)
Most sensitive test for leish what else does it offer?
PCR
Gives a genus too
Rx of limited cutaenous leish in south america? Mucosal?
Sb5 for 20 days
or Amphotericin B
Miltefosine [very expensive]
Only difference with mucusal is longer length of Rx (30 days)
Difference between diffuse cutaneous and disseminated leish?
Disseminated nodular can ulcerate - more like classic lesions
Diffuse dont ulcerate
Diffuse dont ulcerate
Diffuse dont ulcerate
Diffuse dont ulcerate
Diffuse dont ulcerate
Diffuse dont ulcerate
Visceral Leishmaniasis which one if
Mediterranean, Middle east, central Asia and China?
India / east Africa?
South and Central America
L infantum - Mediterranean, Middle east, central Asia and China
L Donovani - India / east Africa
L infantum(syn.L. chagasi) - South and Central America
Leishmaniasis vector? How long inside? What allows the amastigotes to evade macrophages
- Sandfly Takes up amastigotes from an infected host
- Multiply in the stomach of sand fly into promastigotes which takes 1-2 weeks
Sandfly sputum inhibits macrophages (arginine dependent) nitric oxide killing -> promastigotes ingested unharmed by macrophages
- -> reticuloendothelial system
Visceral Leishmaniasis incubation period? Presentation?
- 2-6months usually
- Vague progressive splenomegaly [often massive], hepatomegally, anaemia, wasting, hypopigmentation. Also get ulceration of superficial wounds
Mortality rates Visceral Leishmaniasis
- 100% without rx
- 0-50% with
Visceral Leishmaniasis key ix?
Cheap rapid test? Gold standard?
- Amastigotes on biopsy
- Indirect Fluorescent antibody test (IFAT) Or ELISA
- Rk39 protein ICT test
- Gold standard, - aspirate eg spleen
(ICT = Immunochromatographic tests)
Visceral Leishmaniasis first line rx? In HIV?
- Liposomal Amphotericin B
Add Milterfosine in HIV in India/Africa
Treatment for Visceral Leishmaniasis then few months later develops Macules and papules around mouth may then spread to face and limbs ? Which Rx drug assoc with this?
Rx?
- Post-kala-azar dermal Leishmaniasis
- Sodium stibogluconate
Amphotericin B / milteforsine
[Donovani]
Common reservoir for Leishmania donovani? Bar killing them what can you do?
Dogs - especially in southern Europe
Elsewhere - other livestock
(can use deltametharin-impregnated collars)
Which cutaneous Leishmaniasis resembles leprosy
- Diffuse cutaneous Leishmaniasis
- As unusual to ulcerate, often extensive depigmentation
Symptoms of nasal congestion after Leishmaniasis? Usual bug?
- Mucosal Leishmaniasis - Often years after original infection but can ve at same time
- Progresses and may destroy centre of face
- Viannia sub genus eg. L (V) braziliensis
Only effective way of differentiating vianna sub genus which cause mucosal Leishmaniasis?
PCR
Cutaneous Leishmaniasis 1st line rx if simple and from asia? What if Viannia sub genus or from south america?
- Topical eg cryotherapy /thermal/ imiquimod /paromomycin or amphotericin B
- Sodium stibogluconate
Leishmania sp. amastigotes
Leishmania sp. amastigotes
Leishmania sp. amastigotes
amastigotes are lining the walls of two vacuoles, a typical arrangement.
amastigotes are lining the walls of two vacuoles, a typical arrangement.
Cutaenous leish stain of sample?
Giemsa staining (looking for for Leishmania amastigotes.)
Leish. guyanensis specific rx?
Pentamidine
what am i called
Sandfly - note hairy body + wings
Lutzomyia spp. in the New World
Phlebotomus spp. in the Old World
Which leish if Post-kala-azar dermal Leishmaniasis
Leishmania L. donovani
derm don
Name 2 causes of muco leish
L.V. braziliensis
L.V. guyanensis
L.V. panamensis
L.L. amazonensis
Name 1 old world and 1 new world cause of diffuse cutaneous leish
Old
L.L. aethiopica
New
L.L. mexicana
Lv brasiliensis
L.L. amazonensis
Name 2 causes of disseminated leish
L.V. braziliensis
L.L. mexicana
Name 2 causes of visceral leish
L.L. chagasi/infantum
L.L. donovani
3 vectors of chagas
Triatoma infestans
Rhodnius prolixus,
Panstrongylus
T. brucei gambiense & T. brucei rhodesiense
Indistinguishable to know which one
tsetse fly genus
Glossina
Which Trypanosoma is most likely to have a chancre at presentation
T b rhodesiense - symptoms of systemic disease within 10 days
Gambiense - likely to have occurred months ago (heals in a week)
37M with Fever, Hepatosplenomegaly, and a Cutaneous Foot Lesion after a Trip to Africa,
T. b. rhodesiense trypanosomal chancre
Tsetse bite -> Low grade , intermittent fever
Winterbottom sign -
Edema (face), malnutrition Pruritus, (rash)
T. b. gambiense
Glossina bite ->
Winterbottom sign
T. b. gambiense
Glossina bite ->
Acute high fever, Lymphadenopathies, Edema , rash , petechiae
Multi organ failure
T. b. rhodesiense
face edema looks almost apathetic /malnutrition
T b gambiense
Staging of African trypanosomiasis? When would you count it as positive?
LP
-Presence of trypanosomes in CSF
- Presence of > 5 leukocytes/μL
Oral 1st line for T b gambiense? When would you not use it?
Fexinidazole
- Except if advanced disease/presence of > 100 WBC/μL in CSF, where NECT is still preferred
Most sensitive confirmatory test for gambiense HAT:
Mini Anion Exchange Centrifugation Technique
(mAECT)
How to administer suramin
test dose (100mg) to make sure no anaphylaxis
Then 1g/week for 5 weeks
Medication with a single dose for gHAT
acoziborole
A coz I bor(ed of the) ole (treatments)
Melarsoprol side effects
Polyneuropathy 10%; hepatitis, hemolysis, and encephalitis (5% of people and always fatal)
What’s happened - Rx for visceral leishmaniasis then 3 months later -> Pale spots and painless nodules? Where is is common?
Post Kala-Azar dermal leishmaniasis
- Looks like leprosy
Much more common in Africa (up to 60%)
Compared with India (5-10%)
Differentiate post kala azar from diffuse leish
Number of amastigoites on biopsy
Few in PKAD
Key lab findings in visceral leishmaniasis
Pancytopenia
Hypergammaglobulinemia
Gold standard for diagnosis of Visceral leishmaniasis
Splenic biopsy - key risk of major bleeding (not really practised in wealthy countries)
RDT for visceral leish usually testing for
rK39
[Not very sensitive in east Africa]
Important test before miltefosine rx
Pregnancy - high teratogenicity
[Toxicity frequent but usually mild]
