Future challenges and opportunities in a changing world Flashcards
What is an important thing to consider about parasites?
All our parasites are as evolved as we are as part of a radiation of biodiversity, just evolved in different ways – things in common and things done differently
Time isn’t standing still, that evolution of host, parasite and vector is ongoing and new environmental pressures cause new selection pressures on their genomes.
What are some bad news about the drug treatment?
Difficult, slow, and costly develop
Drug resistance
Insecticide resistance and ecological impacts
Fake and cut drugs
Many anti parasite drugs were discovered > 50 years ago
Parasites are eukaryotes – so their cell structure, genome, biochemistry etc. is like ours – drugs often have severe side effects
What is still the drug of choice against sleeping sickness where there is no cerebral involvement?
Suramin
This was developed in 1916 by Bayer, and is used to treat onchocerciasis and African Trypanosomiasis
The limitations of currently used drugs for main protozoan diseases
What is the good new about the drugs which have been developed?
Mass Drug Administration (MDA) programmes can be successful
Big donors – Big Pharma, Big Government, Big Philanthropy Drug combinations
New drugs, repurposed drugs
Genomics
Integrated control
Targeted intervention
“unlimited supply”
“until global elimination of X is as a public health problem achieved”
“according to WHO requests”
“for as long as needed”
“to eliminate”
100s of millions to billions of doses
Eisai (Japan) – up to 2.2 billion tablets of DEC for lymphatic filariasis over first 7 years, then extended till elimination as public health problem
Onchocerciasis, lymphatic filariasis, trachoma, leprosy, fasciololiasis, paragononimiasis, African trypansosomiasis, Chagas disease, taeniasis, cystercercosis, soil transmitted helminths, schistosomiasis, visceral leishmaniasis
What is some bad new about vaccines which have been developed?
Difficult, slow and very costly to develop
Still very few
Existing ones mainly biological
Species-specific
Animal reservoirs
Parasites have evolved a very wide range of strategies to modulate / avoid / deflect the host immune system
Many under development but many fail at clinical trial
Continuous arms race between host and parasite
Logistics of delivery in much of the world
What is some good news about vaccines which have been developed?
A few effective native vaccines exist in veterinary medicine
A few effective recombinant vaccines exist in veterinary medicine
Veterinary whole organism vaccines show potential for human equivalents
Genomics and other -omics guide target selection
New formulations- adjuvants, conjugation, microencapsulation
RTS,S for malaria in children
Effective native:
- Bovilis Huskvac®, Barbervax® GoTick®
Recombinant:
- Providean Hidatil EG95®, Cysvax®, Providean Aquatec Sea Lice®, GAVAC®
What is some good news in the eye of public health?
Malaria
- Between 2000 and 2015 malaria case incidence reduced by 41 percent and malaria mortality rates reduced by 62 percent. Endemic countries down from 108 to 91.
- In 2020, 26 countries reported fewer than 100 indigenous cases of the disease, up from 6 countries in 2000.
- Since 2015, 9 countries have been certified by WHO as malaria-free: Maldives (2015), Sri Lanka (2016), Kyrgyzstan (2016), Paraguay (2018), Uzbekistan (2018), Argentina (2019), Algeria (2019), China (2021) and El Salvador (2021).
- RTS,S vaccine role out to children in sub Saharan Africa.
- BUT 2020 – 241,000,000 cases and 627,000 deaths, multi drug resistance, multi-insecticide resistance in vector.
Just a couple of examples.
- Visceral leishmaniasis
- 75% decrease from 2005 when the Kala-Azar Elimination Programme was launched to 2014
- The goal of the WHO 2021–30 Neglected Tropical Diseases Road map is to reduce mortality caused by the disease to less than 1%.
What is a consequence of a global world?
It’s a fast-paced, interconnected world we live in and, consequently, things can happen out of the blue and with very rapid and dramatic consequences.
Log scale
https://coronavirus.jhu.edu/data/animated-world-map (edited)
Why is the red queen still running hard?
- Large scale genomic sequencing e.g., with P. Falciparum
- Divergent populations
- Parasite populations are interbred and share genomic halotypes, especially across drug resistance loci
- P. Falciparum from western great apes jumped into humans, prior to major human migrations
- Getts more diverse where transmission high and stable and less where interventions being scaled up
Why is the number of SNP variants so high (29,998)?
- hotspots of variationin regions with known drug response, transportation and metabolism of loci associated with resistance
- chromosome 12 linked to potential resistance loci aganist artemisinin derivates seen in Ghana and Malawi (Artemisinin only discovered in 1971 and used in widespread artemisinin-based combination therapies (ACTS) across Africa since 2006)
What are SNPs related to?
What could this be due to?
SNPs related to drug resistance, erythrocyte invasion, gametocytogenesis, oocyst development, and antigenic loci were the most differentiated between populations.
These could be due to different environmental conditions and varying human and mosquito populations.
Tell me about the re-introduction of parasites, in particular, Malaria
Malaria widely believed to be formerly endemic in UK.
Periodic, febrile illnesses (marsh fever, agues, tertian fevers) historically common in lowland marshland areas of Essex, Sussex, Kent, Somerset Levels, Yorkshire and Lancashire. Probably P vivax or P malariae and probably spread by the indigenous Anopheles atroparvus. – By 20th c was becoming rare due to land drainage and better housing.
1915, WW1, western front in deadlock, Allies decided to open a second front at Salonica (Thessalonika) in the Balkans, where malaria was endemic.
During the campaign, 162,517 service personnel contracted malaria. Many repatriated – est 15-25,000 with active malaria. One of the camps was on the Isle of Sheppey in Kent, an area notorious for marshland fever and mosquitos. Infection took off; 1917-18 270 reported cases. Notification of malaria became compulsory, insecticides were used and standing water cleared. Est 481 cases of P vivax up till 1921, last indigenous case in 1957 (remember the dormant hypnozoites in the liver).
Could it reappear?
What would it need? Parasite and vector
Mosquito
Parasite
Malaria in the UK- imported infection
Only parasite Gov reports official statistics for,
Latest 2019
1719 cases,
1626 England (concentration in London), 58 Scotland, 25 Wales, 10 N. Ireland,
65% male
Mainly UK residents travelling abroad (95%),
Mainly to visit friends or relatives (84%)
Mainly P. falciparum
15 deaths! 14 Pf 1 Pv – parasitaemia at presentation 7-15%
Est. only captured 56% of cases
Notifiable disease but only 11% were officially reported
1 cryptic case with no history of travel!
Across the EU/EEA in 2020, 2369 imported cases (ECDC data) – doesn’t include UK
https://assets.publishing.service.gov.uk/government/uploads/system/uploads/attachment_data/file/989677/Malaria_imported_into_the_United_Kingdom_in_2019.pdf
Dominant anophelese vector species
Tell me about the transmission potential of malaria in the UK
TL Anophelese atroparvus
BR Anophelese messeae
Factor in climate change
But it isn’t just Malaria, and it isn’t just indigenous vectors we have to worry about, as we will see.
Believe it or not, imported schistosomiasis is a major public health issue in the UK – possibly the most prevalent and important imported parasite in UK and very likely significantly underestimated.
Increased global travel and increased travel to exotic places where is endemic
Why is it a problem?
Tied in with life cycle
Skin penetration by cercariae can occur in <15 mins
Lung stage, liver pairing, migrating, mating, egg laying takes several months, long term survival producing 100s-1000s of eggs a day for years, asymptomatic for a long time after return
Schistosomiasis in the UK
No official UK government statistics, but several large-scale longitudinal studies.
Alexander et al 2017 – looked for schistosome-specific antibodies by Elisa in 8163 Scottish travellers including 7 groups comprising 182 travellers, 8-12 weeks after returning from endemic regions and between 2001 and 2015. Need to wait that long.
Overall 25% were seropositive, indicating active infection – albeit largely asymptomatic at that stage,
In the groups who travelled together, overall 35% positive, in 1 group 60% seropositive
in another study of a single school group 13 out of 16 (81%) seropositive (Currie et al. 2018)
Predominantly young adults and predominantly female.
Completely different demographic to malaria where older males of BAME ethnicity visiting fiends and family
Predominantly acquired from Africa, and especially Malawi and Uganda, countries with strong official ties to Scotland including Scotland-Malawi Partnership, Malawi Development program, VSO. UK tourism to Uganda increased > 5 fold in recent years
Increasing over time as more travel to more exotic countries, despite public awareness campaigns and Government recommendations for testing on return, so largely picked up through self referral and likely greatly underestimated and repeated in many other non-endemic countries.
No known transmission in Scotland (no snail intermediate hosts) BUT positive cases seen in group of travellers returning from Lithuania, not a known endemic area!
A longitudinal study by Hospital For Tropical Diseases in London, from 1997 to 2012 by Coltart et al 2015 recorded 1020 cases. Of the 252 confirmed by microscopy, 74% were S. haematobium.
Italy, The Centre for Tropical Diseases in Verona recorded 272 cases from 2010-2014
Also in other studies, multiple reports in last 8 years of infections being acquired in Corsica – Schistosoma haematobium, S bovis (cattle parasite), S. haematobium-S. bovis hybrids, – 2013 >120 cases, indicating active transmission and established life cycle of S. haematobium of Senegalese origin in endemic Bulinus truncatus. All infected individuals had swum in the same river where B. truncatus was found.
Imported schistosomiasis in China
Last few decades have see a very large Chinese involvement in Africa for infrastructure construction projects, energy, trade. Plus increasing tourism by wealthy Chinese. 2013, est. 1,000,000 chinese workers or tourists in Africa, 3,000,000 by 2019
Wang et al 2020. reported 1979-2019, 335 cases of imported schistosomiasis in China. Often diagnosed late with chronic infection and typical symptoms of bilharzia
22% S. mansoni, all Chinese labourers, often with extended stay in endemic areas and water contact. Presented with pathologies associated with long term exposure and chronic infection – hepatomegaly, splenomegaly, eosinophilia, etc. 88% were egg positive (cf Scottish cases where not, as caught early).
74% S. haematobium, mix of Chinese labourers and immigrant African individuals – typical symptoms of urinary schistosomiasis, 27% egg positive. Infection often misdiagnosed as other diseases.
Tell me about the schistosome biogeography and evolution
S mansoni Africa, S America C America and Caribbean
Biomphalaria snail host – evolved in S America but also pan-Africa distribution with lots of species
Map the trees of parasite and host
S. American snail host is ancestral to African hosts
Long distance colonisation of Africa by Biomphalaria from S America somewhen in last 1.8-3.6 million years through transoceanic colonisation (in bird feathers or on vegetation rafts?)
Once in Africa, spread as self-fertile hermaphrodite and became permissive host for endogenous schisto which evolved and speciated.
S. mansoni in New world – very recent
Webster, Gower, CO1 and microsatellite analysis:
600 S. mansoni samples, very diverse and rapidly evolving
Origin of S. mansoni in E Africa
links S. mansoni isolates from Brazil to W African isolates.
Tell me about an imported schistosomiasis vector
- B. straminea from South America –> Hong Kong –> Mainland China and Caribbean
- Most likely escape from lab, become second vector species in the area
- B alexandrina, more compatible with local S. mansoni and more rapid parasite development (co evolved)
- B glabrata, higher cercarial load. The 2 species are now hybridising with potential to yield snails with increased transmission potential.
- B tenagophila has gotten from S. America to Congo and Romania.
- Invasion of B glabrata and B tenagophila both implicated in transmission outbreaks in new homes.
- With imported schisto in China, who knows what might happen….
What are some other imported parasites?
Numerous reports of imported canine linuatulosis (pentastomid / tongue worm) infection in EU, almost invariably tracing back to Romania.
In 2021, the first ever case from a dog in Finland. This dog had been imported from Spain. Lingulata rare in Spain, the last recorded case having been in 2013, so undetected transmission must be occurring.
Molecular typing showed it to be Lingulata serrata.
Change in food habits
Hydatid cyst disease - Echinococcus glanulosus
Pork tapeworm – Taenia solium
Stop animal slaughter on farms
Animals that can be considered for on farm slaughter authorisation must have been bred and reared on the farm/estate and applies only to deer, bison, farmed wild boar, farmed ratites, geese and ducks reared for the production of foie gras and poultry subjected to delayed evisceration.
Or personal consumption by farmer.
Eating raw food…
FDA 2016 Food Safety Survey – USA telephone interview, 2016 4169
Across the 3 surveys over 10 years
40% thought very likely for raw beef to have “germs”
40% thought very likely for raw shellfish to have “germs”
Numbers who thought raw fish very likely to have “germs” decreased from 38% to 31%, numbers eating raw fish increased
48% used electronic devices whilst preparing food, of these only 35% washed hands with soap after touching the device!!
What can one get from Anisakis (Herring worm) and what does it cause?
Anisakis (herring worm) causes anisakidos if live worms eaten in raw, pickled, marinated, smoked, undercooked or improperly frozen fish
(intermediate or parentenic hosts) – also dead worms can provoke severe immune responses and anaphalaxis on repeat exposure.
Fish tapeworm - Diphylobothrium
Liver Flukes - Clonorchis sinensis, Echinostoma
Intestinal Fluke – Metagonimus, Nanophyetus, Heterophyes, Metorchis
Many parasitic diseases are affected by land use changes such as what?
Deforestation
Building of dams
irrigation schemes
urbanisation
How does the change of land use affect parasites?
Clearing of land which would previously have been inaccessible to human use for agriculture, mining or forestry and the transport corridors this opens up displaces wild animals, vector species and the parasites they carry and brings them into contact with humans, increasing risk of opportunistic infection or host switching.
Clearing forest patches in the amazon rain forest and building of roads into those areas expanded the amount of forest edge and the number of warm, partially-shaded pools which created ideal breeding sites for Anophelese darlingi, the most important malaria vector in the Amazon.
Clearance of areas close to prime forest used for agriculture can also attract animals out of the forest to abundant food sources, bringing pathogens with them. In Liberia, forest dwelling mice were attracted out into palm oil plantations, where they shed urine or faeces containing Lassa virus, leading to major outbreaks of Lassa fever.
Trade in wild animals, often illegal and linked to logging and forest clearing, also increases the risk of contact with exotic pathogens and disease transmission.
Deforestation also contributes to climate change and its additional, knock-on effects on parasites and vectors which we will come on to later.
How does water development affect parasites?
Of the 700 million people at risk from schistosomiasis, approximately 100 million live in proximity to large dam reservoirs and irrigation systems.
As seen previously, the 3 gorges dam project in China with the 600km long lake that formed behind it, brought major concerns about increased marshy habitats for the snail intermediate hosts of S japonicum, about preventing the annual flushing of the river which decreased snail numbers and about increased water contact by humans exploiting the new lake for fishing, irrigation, recreation etc..
Threatened to push back major advances in schisto control over 40 years
However this hasn’t happened…
Dongting Lake, a 1,600-square-mile body of water, downstream, home to 48% of the snails in China, including Oncomelania host of Schistosoma japonicum. The snails live in the lake’s vast marshlands, but their populations have plummeted since the Three Gorges Dam - between 2003 and 2015, the area saw a reported 87% reduction in schistosomiasis.
What are some other factors that may come into play with parasite spread and water development?
- Zoonosis with water buffalo (as major reservois host) being replaced by tractors, mass drug treatment, explanded use of molluscicdes etc.
- Contrast that with the Diama dam on Senegal river in W. Africa, built to prevent saltwater getting upstream to increase water available for agriculture.
Blocked annual upstream migration of native river prawns – females need saline estuary to spawn, and young move back upstream that are voracious predators of snail intermediate hosts for schistosomiasis. No prawns = no snail control, by prawns = increased vector numbers
Schistosomiasis rapidly rose from about 10% to >80% of human population.
So, good and bad and case by case
What is some politial instabilities that occur?
No drugs, no vaccine
Breaking the life cycle
Carter Foundation
Dogs and cats are possible reservoir hosts – acting as a barrier to eradication / extinction?
Provide an example of when parasite eradication was a mistake
The Californian condor was at risk of extinction
In 1987 the last 27 wild birds were all captured for captive breeding program – hugely successful, and re-introduction started – currently > 500 free and captive individuals.
BUT, on initial capture each bird was treated with anti-parasitic drugs
As a result, the Californian condor louse (Colpocephalum californici) went extinct
Black-footed ferret (Mustela nigripes) was deloused during captive breeding after extinction in the wild, the ferret louse (Neotri-
chodectes sp.) may have become extinct.
Estimated 40 species of lice are co-endangered with hosts listed on the International Union for Conservation of Nature (IUCN) red list and would face co-extinction.
What are some effects that climate change can have?
How has climate change had an effect on Schistosomiasis transmission?
For all human schisto species, climate change likely to further affect transmission through indirect effects due to poverty, rural subsistence agriculture, lack of sewage systems and access to clean water, lack of affordable healthcare, increasing human movement, dam development and agricultural expansion.
How has climate change affected Chagas disease/
Important to remember that the invertebrate vectors and intermediate hosts of parasites are ectothermic, so changes in temperature alone will affect activity levels and therefore distribution.
Some experiments on the activity level of Triatoma bugs, the intermediate host of Trypanosoma cruzi, which has a strong preference for domestic and peridomestic habitats.
Individuals were acclimatised to hot or cold environments (constant or varying) for 5 weeks and then their activity levels tested at different temperatures.
Response was plastic and nonlinear, which complicates modelling changes in distribution under climate change.
How has climate change had an effect on hookworm and seal mortality?
It’s not just human parasities we should be worrying about.
Increased ocean temperatures affect distribution of fish stocks and foraging regimes of predatory marine mammals.
Study of a nursery for South American fur seals in Chile, the young stay on the beach whilst the mothers hunt at sea and return to nurse.
Hookworm is one of the most serious infectious diseases in young fur seals and sea lions, up to 70% mortality but a strong immune response reduces infectious period and worm burden, resulting in parasite clearance and host survival.
Seguel et al studied seal pup infection rates, growth and immunity in relation to sea surface temperature and its affects on maternal nursing.
How has climate change had an effect on malaria transmission?
Increase in temperature may…
- enhance transmission rates
- widen distribution
- Cause re-emergence in areas with previously controlled transmission or elimination
- Increase in temperature, rainfall, and humidity may cause a proliferation of the vector at higher altitudes where currently absent
- Increased temperatures can block the mosquito stage by reducing rate and intensity of infection and reducing mosquito viability.
At low altitudes...
- At lower altitudes where malaria is already a problem, warmer temperatures will alter the growth cycle of the mosquito and parasite in the mosquito enabling them to develop faster, increasing transmission and thus having implications on the burden of disease.
In dry climates…
- In dry climates, heavy rainfall can provide good breeding conditions for the mosquitoes.
Increased humidity…
- Increased humidity and droughts may turn rivers into strings of pool for mosquito breeding
Heavy rainfall…
- Heavy rainfall can flush rivers and wash away breeding sites
What are some other impacts of climate change that may cause increased susceptibility to malaria?
For example, negative impacts on health, which could contribute to social degradation and economic loss, may result in the inability to seek early diagnosis and treatment or impair control activities such as insecticidal spraying.
The economics are interesting: decreasing malaria transmission by mitigating climatic changes via reduced carbon dioxide emissions, versus using other methods. It is estimated that for the cost of saving one life by cutting down on carbon, 78,000 lives may be saved annually by using mosquito nets, environmentally safe indoor DDT sprays, and subsidies for effective, new combination therapies.
Tell me about the climate change impacts on malaria vector permissiveness
Mordecai et al (2020) looked at data for malarial vs arbovirus fever in Kenyan school children from 2014-2018, in relation to temperature levels.
Data suggest a shift in transmission away from malaria and towards arbovirus at higher temperatures.
Used this to predict effects of climate change on the 2 diseases across Africa.
How has climate change has an effect on bluetongue virus and whagt is this?
Arbovirus infection that causes serious disease in livestock (sheep, goats, cattle and deer)
Sheep are the worst affected - severe fever, swelling and sometimes death. Cattle are frequently carriers
Notifiable disease in UK
Spread by the African midge Culicoides imicola (4mm) can travel >200km on the wind
Higher temperatures can accelerate their lifecycle, increase population size and range and accelerate the development of the bluetongue virus within adults
Rarely found in Europe until 1990s
How has climate change had an effect on bluetongue virus vector range and switching?
Historically, confined to tropical and subtropical areas (Central Africa, South East Asia) but have seen increasing outbreaks in temperate regions.
In 1990s outbreaks in southern Europe linked to expansion of C. imicola host range as a result of climate change, especially warmer warmer winters
Many different serotypes
In 2006, heatwave across Europe, serotype 8 appeared in northern Europe
There it found numerous susceptible, native Culicoides species, which it moved into, allowing further extension of range.
Outbreak lasted 3 years with death of millions of animals (disease and slaughter)
Arrived in UK in 2007 - estimated to have cost £480m, not as bad as it could have been due to:
Arriving in SE were farm and livestock density less,
Heatwave ended and lower than average temperatures
Significant restrictions on animal movements following on 2007 foot and mouth outbreak.
Lucky break
Now considered endemic in mainland Europe
Tell me about how climate change can cause catastrophic events and provide an example
There’s an other side to climate change – increasingly unpredictable and increasingly severe weather patterns with the potential for catstrophic impacts.
This is Cyclone Idai, which hit coastal area of Mozambique, then moving inland to Zimbabwe and Malawi in March 2019. It was one of the worst tropical cyclones ever recorded, killing about 700 people and affecting an estimated 2,000,000 people.
Houses, farmland and roads were swept away by severe floods,, completely disrupting communications, transport, food supply, sanitation systems, heath provision and society in general, a literal and metaphorical perfect storm.
It created an immediate upsurge in infectious disease, further overwhelming the constrained health system in the affected areas, with many health centres destroyed, damaged or disrupted. Cholera outbreak (\>6700 cases in 2 months following the cyclone)
Increased diarrhoeal diseases in areas with limited access to safe water and uncontaminated food;
acute respiratory infections in overcrowded shelters;
leptospirosis and tetanus through exposure to contaminated environment;
vector-borne diseases such as malaria, dengue and other arboviral infections when receding waters generate additional mosquito-breeding sites (15000 malaria cases in first 2 months, approximately 1 million mosquito bed nets needed (UNICEF procured 500,000 and distributed more than 116,000 in first 2 month), schools and health treated with disinfectant and insecticide
Limited power supplies affecting the cold chain needed for some drugs.
And of course, it also killed 1000s of livestock with knock on effects on food production. Surviving animals were sick, injured and starving as many animal owners have had no choice but to flee, leaving them to fend for themselves, equally at risk from flood-related parasitic disease.
Vaccines good news
Integrated control- good news
What are the pros of big data sets?
Better surveillance
- Tracking disease across place and time
- Allows for optimised targeting of control / eradication measures
- Show the impact of current funding, value for money and attract additional funding
Better diagnosis
- Enables rapid treatment
- Enables targeted treatment
- Affected people can be isolated
Better modelling > understanding > prediction
Better preparedness
big data used to track diseases
Use of anonymous cell phone data and high resolution satellite imaging to map population movements
Use of GPS & anonymous cell phone data
Use of social media data / IP addresses
Night-time satellite imaging capturing emitted light reveals seasonal migration
So, what affects parasite distribution?
Eradication programmes
Poverty
Politics
Climate
Movement of intermediate hosts/vectors
Conflict zones (wars, refugee camps, movement of populations)
Emerging diseases
New vector species
Pollution
Urbanization
Ocean acidification
Agricultural expansion and intensification
Changes in water and land use
We need to look at all of these things “holistically”
