erin (L6,12,13)

Question 1

Brucei species

Answer 1

brucei brucei - infect animals
brucei gambiense - infect humans
brucei rhodesiense - infect humans

Question 2

trypanosoma species

Answer 2

Trypanosoma congolense → infection in cattle, high morbidity and mortality
Trypanosoma vivax → global distribution, cattle, tsetse and tabanids, migration of infected animals
Trypanosoma evansi → cattle, global, mostly tabanid fly

Question 3

distribution of:

1. trypanosoma congolense
2. trypanosoma vivax
3. trypanosoma evansi

Answer 3

1. causes bovine trypanosomiasis - in south africa
2. causes bovine trypanosomiasis - sounth africa and south america
3. causes sura - global (asia, south america, north africa)

Question 4

typanosoma brucei statistics

Answer 4

60 million at risk
36 countries
500 000 cases pa
50 000 deaths pa
Less than 10% get treatment
Huge efforts successfully reduced transmission
Reduced in 2015 because of sustained controlled efforts

Not global because the parasite AND the vector have to be somewhere with a good environment

Question 5

VECTOR

Answer 5

TSETSE FLY

well formed vision (so use sight for hunting) BUT NEED LIGHT
Prediahrresis (large blood meal has all nutrients concentrated on it, so release water from the meal to have higher nutrient conc)
Very generalists in biting habits (bite anything with blood… yum)

Very persistent
Opportunity for control - can eradicate well because they dont react well to challenges

Question 6

VECTOR LIFE CYCLE

Answer 6

They have a larvae stage
They dont lay eggs, they lay a fully formed larvae → larvaeparis
The larvae once laid, bury themselves under the dirt - this life strategy is called k-strategist (9 days for larvae to go through 2 molts inside the female, hardens their shell underground, sit there for 30 days before emerging as an adult fly)
(k strategists is opposite of r strategists)

LIFE CYCLE OF 6-14 WEEKS (3 weeks for parasites to develop in host)
Max nmbr of young per lifetime is 8 to 10

Question 7

VECTOR LIFE CYCLE WITH TRANSMISSION

Answer 7

LOOK AT L6 S11

VERY IMPORTANT TERMS TO LEARN

Question 8

Human African Trypanosomiasis

Answer 8

disease progresses through 2 distinct phases:

stage 1 - the early stage (haemolymphatic)
stage 2 - the late stage (encephalitic) sleeping sickness

(early stage associated with blood infection // late stage where the blood brain barrier is crossed and we get to the chronic stage)

Question 9

1. the early stage

Answer 9

(few weeks long, opportunity for early diagnostic and curing)

chancre arises at site of bite in 50% of tb rhodisiense infections
parasite spreads through the lymphatic system and invades the bloodstream

SYMPTOMS

• enlarged lymph glands/spleen
• local oedema
• cardiac abnormalities
• general malaise
• headaches
• undulating fever
• chancre can heal and leave altered pigmentation

Question 10

2. the late stage

Answer 10

parasite invades internal organs including the CNS

SYMPTOMS

• severe headaches
• sleeping pattern affected
• personality changes
• mental functions impaired
• weight loss
• coma and death

neuropathology:
acute haemorrhagic leucoencephalopathy (AHL)
this causes widespread fibrinoid necrosis in the walls of small blood vessels in the affected regions of the brain

Question 11

pathology of Tb gambiense VS Tb rhodesiense

Answer 11

Tb gambiense
long asymptomatic period of months to years.
emerging disease advanced
necessitates early diagnosis

Tb rhodesiense
acute virulent infection
incubation of 1 to 4 weeks
quickly detectable

2 phases occur for both species for HAT tryp
Each associated in a slightly diff way
Parasites in the blood are exposed to the immune response for a long time so there is no acquired immunity which means that we have no vaccine.
No vaccine for chagas either
Death without treatment

Question 12

what is VSG

Answer 12

VARIANT SURFACE GLYCOPROTEIN
They have a mechanism of using decoy antigens

• it covers the entire parasite surface including the flagellum
• 10^7 copies per cell
• the molecule is highly immunogenic
• it elicits strong antibody response from the infected host (so is Highly antigenic)
• stage-specific expression

Question 13

which ? will express VSG?

also explain how it hides from the immune system.

Answer 13

TRYPOMASTIGOTE
immune system will make a response, parasite will switch its surface protein (to protect what is underneath that cannot change) immune system cannot recognise it anymore
CYCLES THROUGH DIFFERENT PROTEINS

Question 14

how is VSG a decoy antigen

Answer 14

ithe parasite swicthes VSG expression
there are&raquo_space;200 VSG genes
these are under transcriptional control

Highly conserved n terminal domain
Only one is transcribed at a time (after some time, coat switches and whichever parasite isnt seen by the immune system will populate inside the host)

Question 15

compare the 2 parasite species that cause HAT

(endemic in _ countries
_% of reported cases
\_\_ disease, lasts for \_\_
\_\_ transmission
\_\_ vector
\_\_ if untreated)

Answer 15

T B GAMBIENSE
endemic in 24 countries (west and south africa)
90% of reported cases (worldwide)
chronic disease, lasts for years
person to person transmission
riverine tsetse vector
fatal if untreated

T B RHODESIENSE
endemic in 13 countries (east and south africa)
10% of reported cases (globally)
acute disease, lasts for months
zoonosis transmission
savannah tsetse vector
fatal if untreated

Question 16

comparative epi-ecology of HAT

Answer 16

LOOK AT L6 S23

Question 17

3 species groups for the spread of HAT

Answer 17

mortisans group (savannah woodland, highly mobile, visual cues)

fusca group (humid forest ecology)

palpalis group (riverine woodlands, less mobile, visual cues)

Question 18

the 3 animal trypanosomes symptoms

Answer 18

they cause subacute, acute, chronic disease
anaemia, intermittent fever, diarrhoea, rapid loss of condition, death
(( Brucei is acute
Congolense is very severe
Vivax less pathogenic but mortality rate can reach 50% ))

TB BRUCEI
cattle incubation 5-10 days
acute in donkeys, horses, no acquired immunity with age

T CONGOLENSE
cattle incubation 4-24 days
single important cause in africa
major cause in cattle in africa
no acquired immunity with age

T VIVAX
less pathogenic than t congolense
incubation 4-24 days
most important in cattle (west africa)
partial acquired immunity with age

Question 19

nagana - severe emaciation

Answer 19

Within a week of infection, there is a decrease in all the cells in the blood (Hg, rbc, wbc etc)
Tac volume increases by 50%

Can cause:
Loss of conditions
Subsequent infertility

Severity of clinical response depends on the severity of the disease and the species of the cattle
Very difficult to replicate this in the lab because the animals are not in natural environments

AGRICULTURAL PRODUCTION LOSSES

Question 20

control measures to reduce transmission

Answer 20

parasites

• resistant breeds (cattle)
• chemotherapy

tsetse flies

• traps
• insecticides
• sterile insect technique

There are 2 drugs to treat cattle
One of them has been used for 50 years so they are now resistant
Resistant breed of cattle

Question 21

vector control rationale

Answer 21

low density of 1 per 1.4m bush
low reproductive potential (8 offspring per 10 day cycles)
4% sustained mortality of femaled per day
should cause extinction

Question 22

different approaches to control HAT

Answer 22

LOOK AT L6 S30

VERY IMPORTANT

Question 23

cheap standard tsetse traps

Answer 23

electrified black target with flanking net
biconical trap with flanking electrified grid

Only takes a small and sustained reduction in the number of female that have a marked impact on the overall population
Because they have a low reproductive potential
Traditionally, the control measure for tsetse was to destroy the larval site

Question 24

insecticide applications

Answer 24

traps
dips or pour on (topical treatment)
individual protection and no mass effect on tsetse population
ultra-low volume spraying

ULV - non residual insecticide
Teste can be very sensitive to some insecticides
Will only affect the present generation

Serial aerosol technique (SAT) to kill the adults. Then spray again in 9 days to kill the next generation (larvae bean grows in 89 days)
Very dependent on climatic and ecological conditions to decide whether we can use these techniques again

Question 25

sterile insect technique (SIT)

Answer 25

been used on zanzibar 1988 tsetse population was suppressed using insecticide treated cattle and traps serial release of sterelized males by aircraft 1994-1997 more than 8.5 million males released Mass release of sterile males They will mate with wild females They can only mate once Her offspring will not develop costs $8 millions

Question 26

PATTEC

Answer 26

pan african tsetse and trypanosomiasis eradication campaign sterile insect technique SIT component up to 4 different species of glossina coexist cost of $6 million per 1600 km / total costs $67 billion requires 350 000 years to eradicate 22 species

Question 27

overlap of HAT sub species

Answer 27

Tb gambiense and Tb rhodesiense Overlapping regions of interest where gambiense and rhodesiense can coexist This is a problem because: Treatments are different The 2 diseases present differently, so diagnosis becomes more difficult People can have both diseases at the same time

Question 28

3 major epidemics of human sleeping sickness

Answer 28

``` - 1900s a third of the population dead survivors evacuated from congo? - 1940s 2 432 cases 274 dea from zambia via Tz? - 1980s 7 000 - 9 000 cases ``` fly biting preference (human 9%, cattle 23%) cattle are 234x more likely source of human Tb rhodesiensis than are humans 20% of cattle need treatment to achieve R0<1

Question 29

increase in area affected by tb rhodesiense and gambiense

Answer 29

Expanding region of disease incidence in northwest and southeast caused by the 2 different HAT 2 regions that are geographically distinct, now they are only 50km away from each other, so getting closer to an overlap Spread of disease is because of domestic cattle movement, and restocking Political instability so movement of people Infected from south to north, expand the infected range

Question 30

SOS initiative

Answer 30

Stamp Out Sleeping Sickness initiative public private partnership launched in uganda 2006 response to possible convergence of Tb rhodesiense and Tb gambiense in N uganda WHY - treatment where human infection are mixed is more difficult EARLY STAGE DISEASE 1ST LINE DRUGS - suramin efficacious against Tb rhodesiense Pentamidine efficacious against Tb gambiense, not rhodesiense LATE STAGE DISEASE 1ST LINE DRUGS - melarsoprol efficacious against both late stage treatment failures of gambiense increasing an alternative is eflornithine but is not effective again rhodesiense

Question 31

SOS initiative | aims, achievements, lessons learned, who pays?

Answer 31

AIMS cleaning cattle through treatment prevent tsetse reinfection by regular spraying of legs and belly (and ears for ticks) ACHIEVEMENTS during 8 weeks of initial emergency intervention, treating cattle in uganda reduced the prevalence of rhodesiensis in cattle by 70% LESSONS LEARNT it works cost effective - RAP is $0.6 per head per month WHO PAYS livestock owners decentralised bottom up approach

Question 32

it is necessary to consider effects on tick borne diseases TBDs of livestock

Answer 32

LIST OF DISEASES IN L6 S43 Our livestock is infected by other diseases (infected by ticks) Many important diseases in our livestock impact their health, isnt great to treat with insecticides, it means it has a knockon effect on all diseases An outbreak of just theileria had an economic impact of millions of dollars (less than trypanosomes)

Question 33

TBD example

Answer 33

BABESIA most infect cattle very pathogenic hall have a tick vector

Question 34

babesiosis in cattle

Answer 34

Red water fever incubation 3-21 days high fever, anorexia, seek shade, weight loss, abortion, poor milk production extensive erythrocytic lysis, 75% rbc destroyed in few days most survive, but mortality is up to 50% carrier status low parasitaemia can last for years

Question 35

cattle babesiosis tick vectors

Answer 35

babesia pass into the ovaries and eggs parasites migrate to the salivary glands of cattle to reproduce in larvae larvae await on grass stalks to attach to cattle babesia from salivary glands injected into the mammals bloodtsream

Question 36

complexity of insecticide treatment of cattle for babesia

Answer 36

insecticides kill both ticks and tsetse need to maintain tick exposure while preventing tsetse bites insecticides cost a lot

Question 37

breed selection conflict | TBD vs Tryps natural tolerance

Answer 37

Bos taurus susceptible to Babesia, but is trypanotolerant Bos indicus is more resistant to Babesia, but very susceptible to Trypanosomiasis and Anaplasmosis SO: - Choose specific breeds to be very susceptible to babesia - Zebu cattle are very common, known for meat quality and for resistance

Question 38

TBD endemic and enzootic stability

Answer 38

- disease is more likely or more severe in older than younger susceptibles - following infection, the probability that subsequent infection results in disease is reduced these criterion met by babesiosis, cowdriosis and anaplasmosis uncertain for theileria nagana - age not related to severity and no conferred immunity

Question 39

immunity to the tick borne diseases

Answer 39

The tick borne diseases are more likely to be severe in older than younger cattle Important for young cattle to be exposed so that they can build up an immunity so that when they get infected at an older age, they won’t die Instead of becoming an epidemic, there is a constant level of circulation that we want to maintain to ensure immunity If we treat all cattle with insecticide, all cows will become very susceptible at an older age

Question 40

measures to take to maintain endemic stability

Answer 40

- tsetse is more susceptible to pyrethoid treated cattle than are ticks, increasing intervention interval lowers impact on ticks - tsetse preferentially feed on different sites of body, particularly legs, avoid tick attachment sites so just apply insecticides on the legts to not affect the ticks on top of the cattle helps with cost too

Question 41

solutions towards sustainability by farmers

Answer 41

tsetse preferentially feed on older and larger herd members-leave young cattle untreated to become exposed to ticks treat half the herd, applying insecticide to only the larger individuals (only slightly less effective, but will greatly reduce the amount of insecticide used) selective treatment of hosts with Restricted Application Protocol (RAP) reduce insecticide costs by 90%, compared with the current regime of treating the entire herd, and the impact on non-target organisms

Question 42

vector control in the absence of cattle

Answer 42

DO I NEED TO KNOW THIS? | L6 S56

Question 43

tiny target traps case study

Answer 43

L6 S57 to S65

Question 44

HAT transmission statistics

Answer 44

normal host infectious period for gambian HAT is 3 years a 72% reduction in tsetse numbers will stop HAT transmission (R0<1) this study approach routinely achieve 90% reductions elsewhere 80% reductions in tsetse populations have impacted on HAT transmission R0 is less than one - disease will die out R0 is more than one - still spreading There is interaction with how long people are infectious for If treatment is very effective, then we only need to have a small impact for the disease to die out → so it is integrated control

Question 45

tiny targets conclusions WHO elimination initiatives - progress simulation model predictions of HAT elimination HAT references

Answer 45

L6 S67-72