case studies of japanese encephalitis virus and east ... · rift valley fever virus in kenya i....
TRANSCRIPT
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Vector-borne diseases in a changing world
Case studies of Japanese encephalitis virus and East African arboviruses
Kansas State University
August 21 2014
Johanna Lindahl
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How to squeeze as much as possible into a presentation:
1. International Livestock Research Institute
i. What does ILRI do?
ii. What do I do for ILRI?
2. Introduction: EIDs, vectors and why we have a problem
3. Japanese Encephalitis Virus in Viet Nam
i. Background JEV
ii. Studies and results
4. Rift Valley fever virus in Kenya
i. Background RVF
ii. Studies and results (so far)
5. Dynamic drivers of disease in Africa
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International Livestock Research Institute Consultative Group for International Agricultural Research
2 Departments:
Integrated sciences
• Food safety and zoonoses
Biosciences
Nairobi
Main campus Nairobi
Second campus Addis Ababa
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CGIAR Research Program
Agriculture for Nutrition and Health (A4NH)
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Agriculture for Improved Nutrition & Health
12 CGIAR centers IFPRI
ILRI
BIOVERSITY
CIAT
CIMMYT
CIP
ICARDA
ICRAF
ICRISAT
IITA
IWMI
WORLD FISH
1. Leveraging value chains for nutrition
2. Biofortification of staple crops: Harvest +
3. Agricultural associated diseases
4. Evaluating nutrition outcomes in programs
4 Themes
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1. Food Safety
2. Emerging infectious disease
3. Neglected zoonoses
Agriculture associated disease
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CGIAR Research Program
Livestock and fish- More meat, milk and fish for and by the poor
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My main projects
1. DDDAC
i. RVF
ii. Cross-sectional socio-economic
2. Aflatoxins
i. Aflatoxin risk assessment Kenya
ii. More aflatoxin stuff (Uganda, Vietnam, India, Senegal, etc)
3. Dairy in India
i. Hygiene project
ii. Tuberculosis, brucellosis and antibiotic resistance
4. Upcoming
i. Vector and water associated diseases in SEA
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An introduction to disease emergence and anthropogenic influences
• Humans are affecting every part of this planet
– Directly or indirectly
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2 billion hidden hunger
The world today
7 billion people
One billion hungry
1.7 billion overweight/obese
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Livestock is important
• 24 billion livestock
After rice, second most important source of food
19 billion in developing countries
1 billion poor people depend on livestock
600 million in South Asia
300 million in Sub-Saharan Africa
25% urban
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There is a business case for one health
• Zoonoses sicken 2.4 billion people, kill
2.2 million people and affect more
than 1 in 7 livestock each year
• Cost $9 billion in lost productivity;
$25 billion in animal mortality;
and$50 billion in human health
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Infectious diseases- historically important
• In 1918-1920 Spanish flu:
• 50- 100 million humans
• Late 19th century Rinderpest:
• Death of 2/3 of Maasai population in Tanzania and Kenya
• Early 19th century Potato blight:
• 25% of Irish population starved or migrated
• 1967: "…war against infectious diseases has been won“
• US Surgeon General William H. Steward
FAO/G.R. Thomson
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HIV, TB, malaria
Other infectious
Mat//peri/nutritional
Cardiovascular diseases
Cancers
Other NCD
Road traffic accidents
Other unintentional
Intentional injuries
0
5
10
15
20
25
30
2004 2015 2030 2004 2015 2030 2004 2015 2030
Dea
ths
(mill
ion
s)
High-income countries
Middle-income countries
Low-income countries
Mortality: global projection, 2004-2030
US Surgeon General William H. Steward was wrong
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Disease emergence?
• Which diseases? • EID twice as likely to be zoonotic than non-zoonotic (zoonotic viruses
and protozoa had highest proportion)
• Quick mutations- typically ssRNA
• Where? • rapid intensification, increasing interactions between animals, humans
and ecosystems, often rapidly changing habits and practices
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Livestock
Wildlife Humans
Ecosystem
LH WL
WH
X
Disease transmission Spillover event
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WNV
WNV
Malaria
Malaria Malaria
Dengue
Dengue
Dengue
Dengue
Yellow fever
Yellow fever
TBE
TBE
RSSE
Borrelia
Borrelia RSSE
JEV
JEV
MVE
Ross River
SLEV
VEE, EEE, WEE
VEE
Bluetongue
Bluetongue
African horse sickness
African swine fever
African swine fever
Chikungunya
Chikungunya
JEV
Babesia
Babesia
Anaplasma, Chikungunya
Sleeping sickness
Chaga’s disease
RVF, WNV Chikungunya
Climate & climate changes Globalisation Urbanization Land-use changes
Why are vector-borne diseases emerging?
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k= Probability that a vector feeding on an infected host gets infected.
Pf = Probability that a vector survives from one meal to the next.
Pe= Probability that a vector survives the Extrinsic incubation period, EIP
Q= Probability that a vector feeds from the right host – blood index for the host.
HBr= Host biting rate, the number of vectors feeding from an animal per day.
v= Probability of pathogens becoming infectious in the vector
C= Vector capacity
C= HBr Qvk Pe/(1- Pf)
Vector capacity and competence
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Japanese Encephalitis Virus- risks with urban agriculture
Infectious disease driver: urbanization
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Is urbanization important? Why is it a driver of disease?
• 7 billion people
• 50% urban inhabitants – continuous urbanisation
• It involves approximately 800 million people and produces 15-20 % of the food in the world
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Urban inhabitants need food
• Large problems to supply from rural areas
• Difficulties with cold chain
Johanna Lindahl Swedish University of Agricultural Science
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The benefits and problems
• Local markets with living and dead animals
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• Possibility to use urban wastes and waste water
• Lacking sanitation
The benefits and problems
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Pathogens in the urban agriculture
• Food-borne pathogens
• Zoonotic animal diseases
• Vector-borne diseases
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Japanese Encephalitis Virus
• Flavivirus, + ssRNA
• Known to be a rural disease
C prM E NS1 NS2A NS2B NS3 NS4A NS4B NS5
Non structural proteins
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Genotypes distribution and spread
1,2,3,4,5
1,2
1,2,3 3
1,3
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A Flavivirus
• Culicidae, genus Culex – Culex pseudovishnui
– Culex tritaeniorhyncus
– Culex gelidus
– Culex fuscocephala
– Culex annulirostris
– Culex quinquefasciatus
…and an Arbovirus
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Disease in humans and horses
• Often asymptomatic
• Incubation period 6-10 days
• Fever, headache and meningitis
• Acute flaccid paralysis
• Coma, death
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JEV and reproduction- pigs
• SMEDI: Stillbirth, Mummification, Embryonal death, infertility
• Middle third of pregnancy most affected
• Immunocompetence after 65-70 days
• Boars: orchitis, aspermia
• Can be experimentally venerally transmitted
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Geographic spread
Population density
(FAO stat estimates)
•3 billion live in
endemic areas
•50 000 cases per
year
•Case fatality 30%
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Our project in Vietnam
• 84 million inhabitants
• 1 600 km from North to South
• Two delta regions
– Red river delta in the north
– Mekong delta in the south
• A cooperation with the Can Tho university
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Ninh Kieu district-Can Tho city
• Around 4800 pigs on 288 pig farms
– <17 pigs per farm
– 1-2 sows
• No poultry reported
• Not many paddy fields
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Ninh kieu district, ”Can Tho city”
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Mosquito collections
Johanna Lindahl
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Collected mosquitoes
• Culex tritaeniorhynchus (36%)
• Culex gelidus (24%)
• Culex quinquefasciatus (15%)
Johanna Lindahl
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Pigs and mosquitoes
Graphs showing the mosquitoes collected in households with and without pigs in Ninh Kieu district, Can Tho city, Vietnam.
Collections made close to humans are shown with thin boxes and collections close to pigs are shown with thick boxes.
A; total number of mosquitoes, B; Culex tritaeniorhynchus C; Culex gelidus D; Culex quinquefasciatus.
Circles depict outliers > 1.5 x the interquartile range and stars extreme outliers > 3 x the interquartile range.
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Serum from urban pigs • Competitive ELISA
• All seropositive
Johanna Lindahl
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Conclusions
• The urban Ninh Kieu district is densely populated with extensive pig keeping
• Most mosquitoes at urban households are potential vectors
• Pig keeping increase the number of vectors
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JEV- infected mosquitoes
Johanna Lindahl
Household with JEV-positive
mosquito pool close to pigs
Household with pigs,
no positive pools
Household without pigs,
no positive pools
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Genotypes
Johanna Lindahl
M18370.1| JaOArS982
U14163.1| SA14
U47032.1| p3
AY585242.1| K87P39
GQ902063.1| KPP82-39-214CT
AF075723.1| GP78
AY508813.1| JaOH0566
AF098735.1| HVI
AF098737.1| TL
AF069076.1| JaGAr 01
AF254452.1| CH1392
AF254453.1| T1P1
AF080251.1| Vellore P20778
EF571853.1| Nakayama
Household D fall
Household T fall
Household D spring
Household S nr 2
L48961.1| Beijing-1
L78128.1| Ling
Household I Spring
Household S nr 1
GQ902061.1| B-1381-85
Household X rural
GQ902058.1| B-0860/82
GQ902059.1| 1070/82
GQ902060.1| 3KP''U''CV569
JF499790.1| TC2009-1
GQ902062.1| 4790-85
JF499789.1| YL2009-4
AB051292.1| JEV
AB241119.1| JEV/sw /Mie/41/2002
AY316157.1| KV1899
AF045551.2| K94P05
AF217620.1|FU
HQ223286.1| WTP-70-22
AY184212.1| JKT6468
HM596272.1| Muar
|JF915894.1| XZ0934
91
86
85
82
68
53
43
37
63
55
48
48
29
19
27
33
32
30
34
48
42
36
34
24
16
39
27
43
99
0.01
III
I
II IV
V
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JEV infection rate
7885 mosquitoes, 352 mosquito pools, 7 positive
Johanna Lindahl
Positive pool
9 Cx. tritaeniorhynchus
39 Cx. tritaeniorhynchus
25 Cx. tritaeniorhynchus
30 Cx. quinquefasciatus
50 unsorted
50 unsorted
50 unsorted
Minimum infection rate per 1000 mosquitoes
All mosquitoes 0.89
Females (including unidentified mosquitoes)
0.98
Cx. tritaeniorhynchus 1.59
Cx. quinquefasciatus 1.27
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Conclusions
• Important with high sensitivity to circumvent inhibition in the PCR
• Both genotype I and III can circulate within the same city
• One per thousand mosquitoes can be infected in an urban area
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Infectious disease driver: Land use changes
Rift valley fever- Risks with irrigation
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RVF
• Bunyaviridae, phlebovirus
• High mortality, abortions in ruminants
• Hemorrhagic fever, encephalitis in humans
• Arbovirus- but also directly transmitted
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Why irrigation?
• More and more range lands in Africa are being converted to crop lands through irrigation to alleviate food insecurity
• Results: major trade-offs in ecosystem services
More food produced (provisioning services) at the expense of biodiversity and regulatory services (disease, flooding, erosion)
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Anthropogenic action:
Increased irrigation
Effect on ecosystem:
Creates more larval habitats
Vector consequence:
More infected vectors
Epidemiologic consequence:
More individuals exposed
Increased
disease
Most drivers are desired- and not constantly leading to disease
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Hypothesis
• Irrigation in an arid and semi-arid area increases the risk for RVF
• But other diseases can also be affected by this…
• … and the doctors don’t know if it is RVF
Study site with stagnant water in irrigation canals – source of water for the locals but also breeding grounds for mosquitoes
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Solving that problem
• Including possible differential diagnoses:
– Leptospira, Q-fever, malaria, WNV, Dengue, Chikungunya, Crimean-Congo hemorrhagic fever, Brucella
Pastoralists in the study site
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Components
• Cross-sectional
– Humans
– Livestock
– Mosquitoes
– Wildlife
– Ticks
• Longitudinal
– Human febrile cases
– Livestock- shoats
– Mosquitoes
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•The study site:
– Tana River and Garissa counties, northeastern Kenya
!.
!.Bura
Hola
0 10 20 30 405Kilometers
´
Legend
Settlements
Irrigation Schemes
permanent
mixed
temporary
!. Towns
Study Block
Tana River County
Tana River
Other Rivers
Riverrine Forests
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Mosquitoes trapped – relative abundance and species distribution
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0.00
0.10
0.20
0.30
0.40
RVF WNV Dengue
Irrigateed area
Non-irrigated area
Disease
Sero
pre
vale
nce
Samples screened – 481 samples have been
screened so far
– Questionnaires administered to 430 households
Serological tests
– WNV and Dengue sero-prevalence apparently higher than that for RVF though confirmatory are yet to be done
Relative seroprevalence of RVF, WNV and Dengue
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Risk factor analysis - findings
For WNV and Dengue model:
I. Males have a higher risk of exposure than females
II. Farmers have a higher risk compared to pastoralists
For RVF model:
I Males have a higher risk of exposure than females
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• Build capacity on differential diagnosis of febrile illnesses in the local health centres. Currently, most cases are treated as:
– Malaria
– Brucellosis
– Typhoid
Intervention points
0
0.1
0.2
0.3
0.4
0.5
0.6
Pro
po
rtio
n
Communities’ perceptions on diseases that manifest similar signs as malaria – limited knowledge on arboviruses
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DDDAC
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Case study: Zambia/ Zimbabwe
• Trypanosomiasis/tse tse
• Land use changes
– Protected area
– Area where livestock has been increasing
– Former large-scale farms with low biodiversity
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Case study: Ghana
• Henipa virus/ bats
• Urban –rural migration
• Livelihoods, poverty, ecology and the association with disease
– How do humans interact with bats and what perceptions do they have of the risks
– Protected/sacred area
– Urban area
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Case study: Sierra Leone
• Lassa fever/ multimammate rats
• Land use changes and rodent ecology
– Urban-rural
– Irrigation and precipitation
– Human-rat interaction and risk perceptions
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The perfect model?
Ecosystem health
Human health
Animal health
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Not the end…. ….but the beginning
Open to questions
Open to discussion
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Come visit us
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Come visit us