erin (L6,12,13) Flashcards
Brucei species
brucei brucei - infect animals
brucei gambiense - infect humans
brucei rhodesiense - infect humans
trypanosoma species
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
distribution of:
- trypanosoma congolense
- trypanosoma vivax
- trypanosoma evansi
- causes bovine trypanosomiasis - in south africa
- causes bovine trypanosomiasis - sounth africa and south america
- causes sura - global (asia, south america, north africa)
typanosoma brucei statistics
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
VECTOR
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
VECTOR LIFE CYCLE
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
VECTOR LIFE CYCLE WITH TRANSMISSION
LOOK AT L6 S11
VERY IMPORTANT TERMS TO LEARN
Human African Trypanosomiasis
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)
- the early stage
(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
- the late stage
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
pathology of Tb gambiense VS Tb rhodesiense
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
what is VSG
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
which ? will express VSG?
also explain how it hides from the immune system.
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
how is VSG a decoy antigen
ithe parasite swicthes VSG expression
there are»_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)
compare the 2 parasite species that cause HAT
(endemic in _ countries _% of reported cases \_\_ disease, lasts for \_\_ \_\_ transmission \_\_ vector \_\_ if untreated)
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
comparative epi-ecology of HAT
LOOK AT L6 S23
3 species groups for the spread of HAT
mortisans group (savannah woodland, highly mobile, visual cues)
fusca group (humid forest ecology)
palpalis group (riverine woodlands, less mobile, visual cues)
the 3 animal trypanosomes symptoms
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
nagana - severe emaciation
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
control measures to reduce transmission
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
vector control rationale
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
different approaches to control HAT
LOOK AT L6 S30
VERY IMPORTANT
cheap standard tsetse traps
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
insecticide applications
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
sterile insect technique (SIT)
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
PATTEC
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
overlap of HAT sub species
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
3 major epidemics of human sleeping sickness
- 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
increase in area affected by tb rhodesiense and gambiense
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
SOS initiative
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
SOS initiative
aims, achievements, lessons learned, who pays?
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
it is necessary to consider effects on tick borne diseases TBDs of livestock
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)
TBD example
BABESIA
most infect cattle
very pathogenic
hall have a tick vector
babesiosis in cattle
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
cattle babesiosis tick vectors
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
complexity of insecticide treatment of cattle for babesia
insecticides kill both ticks and tsetse
need to maintain tick exposure while preventing tsetse bites
insecticides cost a lot
breed selection conflict
TBD vs Tryps natural tolerance
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
TBD endemic and enzootic stability
- 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
immunity to the tick borne diseases
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
measures to take to maintain endemic stability
- 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
solutions towards sustainability by farmers
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
vector control in the absence of cattle
DO I NEED TO KNOW THIS?
L6 S56
tiny target traps case study
L6 S57 to S65
HAT transmission statistics
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
tiny targets conclusions
WHO elimination initiatives - progress
simulation model predictions of HAT elimination
HAT references
L6 S67-72
