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.
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 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.
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.
Vaccines good news
Integrated control- good news
