Malaria + Schisto - 17 - 22 Flashcards
1
Q
What is the global epidemiology of malaria?
A
Based in subequatorial regions of the world, in particular LICs
WHO 2017, 445 000 deaths worldwide
2
Q
How and why has the epidemiology of malaria changed in the last 15 years?
A
There has been a decrease in deaths from malaria due to large-scale interventions
According to the CDC, malaria mortality has decreased by 25% from 2010-16
3
Q
What is the definition of malaria?
A
Presence of a lot of parasites in the blood AND symptomatic
4
Q
What is the definition of parasitaemia?
A
Presence of parasites in the blood BUT asymptomatic i.e. carrier of parasite
5
Q
What is the life cycle of malaria?
A
1) Female Anopheles mosquito takes a blood meal from the human and injects sporozoites into the blood via anticoagulant saliva
2) Sporozoites travel to human liver where they grow + multiply
3) Sporozoites infect RBCs + destroy them + releases daughter cells - this stage causes the symptoms of malaria
4) Male + female gametocytes form in RBCs
5) Mosquito feeds and ingests gametocytes –> mate in mosquito gut + grow into sporozoites
6) Sporozoites migrate to mosquito salivary glands + cycle begins again
6
Q
What stage of the life cycle causes malarial symptoms?
A
The human blood stage where the sporozoites infect + destroy RBCs
7
Q
What are the 5 different types of malaria parasites?
A
FVM KO P. falciparum P. vivax P. malariae P. knowlesi P. ovale The first three can cause death in humans
8
Q
What is the clinical manifestation of malaria?
A
Very non-specific Fever Myalgia Headache Clinical anaemia Abdo pain + vomiting + diarrhoea
9
Q
What is the gold standard diagnosis for malaria?
A
Thick + thin blood films
Antigen test
10
Q
Who are the susceptible populations for severe malaria?
A
Children < 5
Pregnant women
11
Q
Why are children + pregnant women susceptible to severe malaria?
A
They both have weakened immune systems
Pregnant women also express CSA (Chondroiton Sulphate A) which isn’t usually expressed but only in pregnancy - can cause preterm delivery and low birth weight which lowers health outcome due to insufficient neonatal facilities in countries where this is more likely to occur in
12
Q
What is sequestration?
A
Whereby RBCs block microvasculature so no normal blood can flow through
Parasites hide in knobs of RBCs so doesn’t get cleared by the spleen
13
Q
What is the link between sequestration and malaria?
A
Link between sequestration + severity of disease
14
Q
What is the gold standard treatment for malaria?
A
Artemether - contains artemesinin but there is partial resistance
15
Q
What is the gold treatment for severe malaria?
A
Artesunate
16
Q
What vaccine is currently being developed for malaria?
A
RTS, S
17
Q
What are the 3 pillars of interventions for malaria?
A
Vector control
Chemotherapy
Case management
18
Q
Why was there a plateau in reduction of malaria incidence in 2017?
A
Donor decrease
Resistance
Poor compliance
Difficult to reach poor access people - only ones left now to treat
19
Q
What are the 3 stages of malaria transmission?
A
1) Pre-erythrocytic stage (liver)
2) Erythrocytic stage (blood)
3) Sexual stage (mosquito)
20
Q
What 2 immune effector mechanisms?
A
Early immune phase
Late immune phase
21
Q
What is in the early immune phase?
A
TEP1 marks parasites for lysis/melanisation
22
Q
What is the late immune phase?
A
Expression of NOS by JAK/STAT pathway to kill the paraiste
23
Q
What happens when ookinete transverses?
A
Physical damage and time bomb
24
Q
What are the key barriers in disease control? (x3)
A
Vector
Parasite
Environment
25
What are the vector barriers in disease control?
Mosquitoes are adaptive - behaviour + resistance to insecticide
More than one type of mosquito that can transmit malaria
26
What are the parasite barriers in disease control?
Many species
Adaptive
Plasmodium parasites are complex
Antigenic variation
27
What are the environmental barriers in disease control?
Remote regions and poor
| Malaria is geographically specific
28
What are the 3 categories of opportunities for disease elimination?
Simple methods
Vector
Parasites
29
What are the simple methods to eliminate malaria?
Bed nets
| Insecticides - resistance
30
What are the vector methods to eliminate malaria?
Alter mosquitoes so they can't produce progeny
| Produce progeny that can't transmit malaria
31
What are the parasite methods to eliminate malaria?
Vaccine - RTS, S
| Drugs - increase dose, new compounds and different combo of drugs
32
What are the problems with the RTS, S vaccine?
It is cost-effective but there is variable efficacy
Initial studies in Malawi + Tanzania show that it is cost-effective even at highest price + lowest VE
Decay in efficacy
High initial outlay
Could shift disease burden to older children in areas of higher transmission
Low efficacy
33
Why is parasite replication exponential and periodic?
Merozoite producing multiple daughter cell and synchronous rupture of erythrocytes
When high parasite densities are reached, bursting of RBCs every 2 days leads to periodic fevers
34
What is the gold standard diagnostic test for P. falciparum infection?
Polymerase Chain Reaction
Expensive + time consuming BUT accurate
Rapid diagnostic tests used more commonly as this is expensive but missed cases so still transmissable
35
What are the 3 types of treatment for malaria?
Drugs - Arthemeter
Chemoprophylaxis - daily doses of anti-malarial drugs before being exposed to parasites
Vaccination
36
Why is artemisinin usually given with a partner drug as an Artemesinin Combination Therapy (ACT)?
Artemisinin has a very short-half life despite being very efficacious - recurrent infections causes increased resistance due to short half life
37
What are the advantages of artemisinin combination therapy vs artemisinin monotherapy?
Long half-life of partner drugs prevents recurrent infections
Partner drug provides a period of prophylaxis - individuals protected against new infections for up to a month after treatment
Partner drug protects artemisinin from selection pressure from drug resistance
38
What is artemisinin resistance caused by?
Poor treatment practices
Inadequate adherence to prescribed regimen
Monotherapies
Substandard forms of drug
39
Which countries confirmed artemisinin resistance as of Feb 2015?
```
5 regions of Greater Mekong subregion
Cambodia
Laos
Myanmar
Thailand
Vietnam
```
40
What is required to maintain immunity?
Repeated natural infection
| Acquired immunity is partial + short-lived
41
What are the 3 types of vaccines?
Pre-erythrocytic vaccines
Erythrocytic vaccines
Transmission blocking vaccines
42
How does the pre-erythrocytic vaccine work?
Targets + kills sporozoitesin the skin + liver cells so at the bottleneck before any serious harm caused as there is a finite number of sporozoites
43
What are the advantages of a pre-erythrocytic vaccine?
Ideal 'gold standard' - provides sterile protection by preventing the development of any parasites
Community level malaria transmission reduced through herd immunity if high enough vaccine efficacy and coverage obtained
44
What are the disadvantages of a pre-erythrocytic vaccine?
One sporozoite evading the vaccine-induced immune response is enough for a full episode of malaria
The time sporozoites are exposed to vaccine-induced immune response in skin is very short
45
Give an example of a pre-erythrocytic vaccine
RTS, S - induces CD4+ T cells to target + kill infected cells in the liver
46
How does an erythrocytic vaccine work?
Does not prevent infection but instead prevent episodes of symptomatic malaria
47
What are the advantages of an erythrocytic vaccine?
Can prevent episodes of clinical malaria, severe malaria + death
48
What are the disadvantages of an erythrocytic vaccine?
Does not prevent infection - vaccinated individuals are still parasitaemic so vaccinated individuals can still transmit malaria to others
Unlikely to reduce population level transmission
49
How does a transmission blocking vaccine work?
To induce a human immune response that prevents the malaria parasite from being transmitted from the human to the mosquito
50
What are the advantages of a transmission blocking vaccine?
Can interrupt malaria transmission in a community
51
What are the disadvantages of a transmission blocking vaccine?
No individual level protection - 'altruistic vaccine'
| Useless if high levels of vaccine coverage are not obtained - entirely dependent on herd immunity
52
What is the definition of elimination in terms of malaria?
Interruption of local transmission of a specified malaria parasite species in a defined geographical area as a result of deliberate activities
53
What is the definition of eradication in terms of malaria?
Permanent reduction to zero of the worldwide incidence of infection caused by all human malaria parasite species as a result of deliberate activities
54
What is in the current vector control toolbox? (x4)
Larval Source Management (LSM)
Long-lasting Insecticide Treated Nets (LLINs)
Indoor Residual Spraying (IRS)
Environmental Management
55
What is involved in larval source management?
Larvicides - chemical poisons, bacteria or funghi applied to breeding sites
Griffin et al., 2010 - Outdoor + zoophagic mosquitoes are biggest challenge to malaria eradication
56
What are the advantages of larval source management?
Complements other control strategies
| Can target mosquitoes that bite outdoors and on animals
57
What are the disadvantages of larval source management?
Identifying breeding sites can be very difficult
Larvicide needs to be frequently reapplied (weekly)
Need to consider environmental feasibility
58
How do insecticide treated nets (ITNs) provide individual-level protection? (x3)
Repellency/expellency
Bite inhibition
Knockdown + mortality
Treated with pyrethroid insecticides so completely harmless to humans
LLINs with slow releaseinsecticide effective for 5 years without respraying
59
What are the cons to insecticide treated nets?
Mosquitoes bite outdoors + in evening before people go to bed
Nets have holes
If not tucked in, net ineffective
Nets can come in contact with skin - skin accessible to mosquitoes
Mosquitoes are becoming resistant to the insecticides
60
How does the indoor residual spray work?
Application of a long-lasting insecticide to the inner walls of a house with a hand-compression sprayer
Targets mosquitoes by repelling them from sprayed houses + killing mosquitoes that rest on sprayed walls
61
What are the pros of IRS?
Wider range of insecticides > ITNs
Large areas can be protected quickly by organised spray teams
Results often comparable to ITNs if sufficient coverage
62
What are the cons of IRS?
Often only works for mosquitoes who rest indoors - don't affect outdoor mosquitoes
Spray campaigns logistically challenging
Houses need to be re-sprayed annually
Benefits are only seen if a majority of residents are involved
Many residents oppose insecticide use due to health concerns, can kill beneficial insects
63
What methods can be used in environmental management?
Removal of stagnant water e.g. draining swamps, removing old tyres - not always possible due to rainy seasons
Investing in more secure housing, windows, doors, screens
Monitor agriculture, construction, irrigation as these activities can generate breeding sites
64
What are the cons of environmental management?
Requires collaboration between community members + vector control officers
Difficult to evaluate success of environmental campaigns
65
What strategy is in place currently to combat malaria?
Global Technical Strategy: 2016-2030
66
What are the aims of the Global Technical Strategy: 2016-2030?
To increase funding to achieve $8.7 billion per year
67
What can cause resistance in insecticides?
Physiological - mosquito less likely to be affected by insecticide
Behavioural - mosquitoes that rest outdoors + feed earlier at night
68
What is a potential model to eliminate malaria?
Model of parasite's natural dynamics
Incorporate effects of all the interventions you want to consider
Tailor your model to the ecology of the setting
69
Why is coverage hard?
When coverage is high, increasing coverage becomes increasingly hard
Hard to reach populations e.g. adolescents/migrant populations
Issues of allocation e.g. over-allocation to small households
70
Can malaria currently be eradicated?
Currently malaria cannot be eradicated with the current tools
R0 is too high
Requires more global financial commitment
Would require unprecendented universal political + social commitment
71
What can be done in the future to eradicate malaria?
Global targets to be ambitious
Progress has stalled does not mean zero progress - nets + drugs most cost-effective interventions, many gains are still available
More emphasis on eradication targets aligning with burden reduction targets
Concentrate on horizontally integrated approaches
72
What is the epidemiology of schistosomiasis?
2nd most prevalent infectious parasite disease behind malaria
200 000 deaths a year in SSA (WHO, 2012)
73
How does schistosomiasis transmit?
```
Irrigation fields
Collecting water
Fishing
Washing clothes
Playing
Bathing
```
74
Which population is most susceptible in schistosomiasis?
Children - prevalence + intensity of infection increase with age, peaking in the 5-14 y/o age group
Children suffer the most S/Es of the disease - poor growth + cognitive development
In older people, there is decline in intensity but not prevalence
75
What is the lifecycle of schistosomiasis?
1) Infected person urinates/openly defecates openly into lake/open water
2) Eggs of parasite released + hatch into miracidia (infants)
3) Infects snails + goes into flesh of snails by penetrating tissue
4) Miracidia mature into cercariae - forms tail + explodes out of snail
5) Cercariae penetrate human skin - can't get infected by ingestion as stomach acid kills it
6) Cercariae lose tails + migrate via portal blood in liver
7) Mate to form adults and more eggs
8a) Lodges in tissue which causes symptoms in bladder, liver, kidney, gut, spleen
8b) Infected person urinates + openly defecates in lake
76
What are the methods of controlling schistosomiasis? (x5)
```
Tx with Praziquantel
Health Education
Snail control - chemical, environmental + biological
Improved WASH
Altering water flow + levels
```
77
What are the issues with Praziquantel?
Limited PZQ tablets available
| Non compliance due to bad taste, lack of education, motivation, behaviour + needs to have a full stomach
78
Name 4 interventions under the health education methods of control of schistosomiasis
Teaching materials in school
Accessible toilets close by river/pond
Alternative play areas + games for children
Safe laundry area near river/pond
79
What is the main issue regarding changing behaviour of schistosomiasis?
There is high awareness of disease but poor knowledge about prevention of re-infection
80
What are the different types of snail control?
Chemical - molluscicides
Environmental - unless there is long term commitment from communities there is rapid reintroduction
Biological - introducing pathogens + parasites, predators, competitors + genetic manipulation
81
What are the methods of improved water and sanitation for schistosomiasis control?
```
Bore holes
Pumps
Wells
Piped water
Flushing toilets
Pit Latrines
Adequate water for handwashing
```
82
Name a case study whereby an intervention had an indirect consequence on schistosomiasis incidence
Senegal Diama Dam was built but schistosomiasis reported 130km from the dam - physical + chemical changes led to an increase in snail hosts
Prawns were introduced which consumed a large number of snails
83
How is the disease burden of schistosomiasis usually expressed?
DALYs as people are likely to live with these infections for a long time + bear consequences e.g. anaemia
84
What is needed for a successful program to control schistosomiasis?
```
Endemic country engagement
Financial + programme planning
Mapping of disease prevalence
Training of personnel + capacity building
Social mobilisation/sensitisation
Health education
Distribution of drugs + equipment to district level
Community led distribution
Monitoring + evaluation
```
85
What global strategy is there to control schistosomiasis?
WHO Strategy for Elimination of SCH
1) Control of morbidity
2) Elimination as a public health problem
3) Elimination/interruption of transmission
86
What Imperial based initiative controls schistosomiasis?
Schistosomiasis Control Initiative
| Drugs mostly donated by pharmaceutical companies + government bodies
87
Why is monitoring + evaluation important in schistosomiasis control?
Ensures what needs to be done gets done
Monitoring effectiveness of control programmes
Developing ways of strengthening control programmes
Researching future control + elimination strategies
88
What are the 4 steps in monitoring + evaluation schistosomiasis control?
Process - Data Quality Tool
Performance - found that children who attends school are more likely to receive Tx
Impact - urine filtration + dipstick; circulating cathodic antigen
Value for money
89
What are the challenges in reaching global goals in controlling schistosomiasis?
```
SEAR
Reservoir of infection in the snails
Lack of education
Poor access to treatment
Resistance to PZQ
Prevalence not reduced but intensity increased in high transmission areas over time
```
90
Why are there 'hotspots' of schistosomiasis in Uganda?
High awareness of disease but poor knowledge about prevention of re-infection
Poor awareness of drug distribution
Behaviour change: school attendance, knowledge of disease, pregnant women don't trust the drug, WASH practices
91
What is the future of Schistosomiasis control?
Confirm identified hot-spot areas - observed treatment + response
Define drivers of poor coverage in hot-spot areas
Determine WASH practices
Investigate feasibility of snail control in hot-spot areas if other interventions are implemented at a high level
