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Rift Valley fever in East Africa:
Factors driving emergence, potential interventions
and challenges to effective control
A seminar given at the London School of Tropical Medicine and
Hygiene, London, 2 November 2018
Bernard Bett
International Livestock Research Institute, Nairobi
Outline
• General introduction
• Drivers of RVF
• Interventions
• Concluding remarks
Improved food and
nutrition security for
health
Improved natural
resource systems and
ecosystem services
Reduced poverty
ILRI’s mandate
ILRI’s mission is
to improve food and nutritional security
and to reduce poverty in developing countries
through research for
efficient, safe and sustainable
use of livestock —
ensuring better lives through livestock.
IHH CGIAR A4NH Flagship
Improving Human Health Flagship:
bridging agriculture and public health
research to deliver high quality scientific
outputs and to identify new integrated actions
that improve human health
RVF -- Background
• Rift Valley fever – mosquito-
borne viral zoonosis mainly
affecting cattle, sheep, goats
and camels
• Epidemics -- associated with
above-normal, persistent
rainfall and flooding
• Motivation:
o Overlap select pathogen --
severe threat to human and
animal health
o Epidemics – severe
socioeconomic impacts
RVF virus
• Single stranded segmented genome – L, M, N
• Family Bunyaviridae, genus Phlebovirus
• Remains infective for several weeks in biological samples
stored at 4C
Viraemia and antibody response
Bird et al. 2009
Vectors
• RVF virus vectors classified into maintenance/primary
vectors, and amplifying/secondary vectors
o Maintenance/primary vectors
Floodwater Aedes which maintain RVF virus
through transovarial transmission
o Amplifying/secondary vectors
Over 30 species of mosquitoes from 6 genera
(Aedes, Culex, Anopheles, Mansonia)
• Questions on the maintenance of RVF – endemic
verses transovarial transmissions
Hosts
• Susceptibility of vertebrates to RVF virus infection
(Scientific Panel on Animal Health and Welfare, EFSA,
2005)
Extremely susceptible
(70 – 100% mortality)
Highly
susceptible (20 –
70% mortality)
Moderately
susceptible (<10%
mortality)
Resistant Refractory
New-born lambs Sheep Cattle Equines Birds
New-born kids Calves Goats Pigs Reptiles
Puppies Certain rodents Camels Dogs Amphibians
Kittens African buffalo Cats
Mice Asian buffalo African monkeys
Hamsters Monkeys Rabbits
Certain rodents Baboons Guinea pigs
Humans Certain rodents
• Role of wildlife in RVF epidemiology not clear
Has there been any changes in
geographical range of the disease?
1950s – 1990s 2000 - 2015 2016- now
Drivers • 2000, following heavy
rainfall
• About 2000 humans
infected, 245 deaths
• Thousands of sheep
and goats affected
• RVF virus introduction
linked to livestock
trade
• Evidence of new
transmissions 2004
• C. tritaeniorhynchus,
A. vexans arabiensis
• 1987, 93, 98, 2003
• Heavy rainfall,
following a short
rainless period
• Ae. aegypti, C.
nebulosus, A.
gambiae, C.
quinquefasciatus
• Mar 1990 and Jan
2008
• Livestock movement
from Comoros
• Climate variables not
clear
• 1977 outbreak
• Suspected to be due
to livestock movement
or wind-assisted
migration of
mosquitoes
• Heavy, persistent
rainfall
Potential interventions
• Livestock vaccination – key intervention
• Challenges:
– Vaccine safety concerns
Vaccine Source Challenges
Smithburn Isolated from
mosquitoes in 1944
• Attenuated strain passaged in
mice – associated with
abortions and teratogenicity
• Formalin inactivated – poor
immunogenicity
MP-12 Isolated from a patient
in Egypt and subjected
to serial passages
Hepatocellular degeneration and
necrosis
Clone 13 Recovered from
infected patient on
Central Africa
Crosses ovine placental barrier
leading to foetal infections,
malformations and stillbirths
New vaccines
• Development of new vaccines to address
safety challenges
– adenovirus-vectored vaccine for RVF called
ChAdOx1-GnGc (Warimwe et al. 2013)
– Vector -- replication-deficient chimpanzee
adenovirus, ChAd
– Clones being used code code RVFV Gn and GC
envelop glycoproteins
– Vaccine has passed safety tests but more on-
farm trials being planned
– Jenner Institute, Wellcome Trust-KEMRI, ILRI and
KALRO
Gaps in vaccination strategies
• Current strategy – reactive vaccination which often
fails to achieve required coverage
• RVF vaccines often delivered through state
financing – levels of acceptance variable
• Activities:
- Stakeholder engagements to design new
vaccination strategies e.g. routine vaccination in
the high risk areas
- Studies to understand barriers to vaccination
uptake – gender, knowledge, attitude and
practices
Technical studies to inform vaccination strategies
0 7 10 14 21 28 56 84 112 140 168 196 224 252 280 308 336 364
 Serum
 White blood cells
in RNAlater
 Serum
Days post vaccination
Smithburn
RVF vaccine
• Collect WBC at early time-points for
transcriptomics
• Collect sera at all time-points
– cELISA
– VNT
• Study effects of concurrent infections
Sub-county Vet
Department
Community Disease Reporter
Syndromic surveillance
National DVS
County DVS
•Types of drugs sold
•Reported syndromes
Agro-veterinary shops
Abattoirs
•No. slaughtered/day
•Ante-mortem/PM lesions
&parasites
•Syndromes/rumours
•Disease outbreaks
Livestock owner
Livestock markets
•Syndromes
•Disease outbreaks
•Movement patterns
Surveillance data
• Gaps in surveillance:
– Sustainability
– Levels of knowledge – variable
https://ilvac.net/2018/06/22/introducing-english-and-
swahili-instructional-videos-on-the-patterns-signs-
symptoms-and-control-of-rift-valley-fever/
Statistical and mathematical modelling
• A system/tool for forecasting risk and
identifying hot spots for targeted
intervention
• Evaluate effectiveness of interventions
• Analyse climate change impacts
Species Total pop High risk (%)
Camels 1,054,319 37%
Goats 12,800,000 25%
Sheep 9,941,564 22%
Cattle 12,400,000 27%
RVF risk SD (RVF risk)
Sheep Cattle
Goats Camels
Robinson TP, et al. Mapping the global distribution of livestock. PLoS One.
2014;9. doi:10.1371/journal.pone.0096084
Climate change
Current distribution Predicted distribution
In 2050 - RCP 4.5
Predicted distribution
In 2050 - RCP 8.5
Concluding remarks
• RVF risk likely to intensify in some locations – more
studies to predict future occurrence patterns
• Strategies for deployment of interventions – this has
attracted limited attention
• Co-occurrence with other viruses – e.g. Ngari virus
• Work more with policy makers to improve
effectiveness of response
Acknowledgements
Department of
Veterinary Services
Kenya Medical
Research Institute
University of
Nairobi
Bura Irrigation
Scheme
better lives through livestock
ilri.org
This presentation is licensed for use under the Creative Commons Attribution 4.0 International Licence.

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Rift Valley fever in East Africa: Factors driving emergence, potential interventions and challenges to effective control

  • 1. Rift Valley fever in East Africa: Factors driving emergence, potential interventions and challenges to effective control A seminar given at the London School of Tropical Medicine and Hygiene, London, 2 November 2018 Bernard Bett International Livestock Research Institute, Nairobi
  • 2. Outline • General introduction • Drivers of RVF • Interventions • Concluding remarks
  • 3. Improved food and nutrition security for health Improved natural resource systems and ecosystem services Reduced poverty ILRI’s mandate ILRI’s mission is to improve food and nutritional security and to reduce poverty in developing countries through research for efficient, safe and sustainable use of livestock — ensuring better lives through livestock.
  • 4. IHH CGIAR A4NH Flagship Improving Human Health Flagship: bridging agriculture and public health research to deliver high quality scientific outputs and to identify new integrated actions that improve human health
  • 5. RVF -- Background • Rift Valley fever – mosquito- borne viral zoonosis mainly affecting cattle, sheep, goats and camels • Epidemics -- associated with above-normal, persistent rainfall and flooding • Motivation: o Overlap select pathogen -- severe threat to human and animal health o Epidemics – severe socioeconomic impacts
  • 6. RVF virus • Single stranded segmented genome – L, M, N • Family Bunyaviridae, genus Phlebovirus • Remains infective for several weeks in biological samples stored at 4C Viraemia and antibody response Bird et al. 2009
  • 7. Vectors • RVF virus vectors classified into maintenance/primary vectors, and amplifying/secondary vectors o Maintenance/primary vectors Floodwater Aedes which maintain RVF virus through transovarial transmission o Amplifying/secondary vectors Over 30 species of mosquitoes from 6 genera (Aedes, Culex, Anopheles, Mansonia) • Questions on the maintenance of RVF – endemic verses transovarial transmissions
  • 8. Hosts • Susceptibility of vertebrates to RVF virus infection (Scientific Panel on Animal Health and Welfare, EFSA, 2005) Extremely susceptible (70 – 100% mortality) Highly susceptible (20 – 70% mortality) Moderately susceptible (<10% mortality) Resistant Refractory New-born lambs Sheep Cattle Equines Birds New-born kids Calves Goats Pigs Reptiles Puppies Certain rodents Camels Dogs Amphibians Kittens African buffalo Cats Mice Asian buffalo African monkeys Hamsters Monkeys Rabbits Certain rodents Baboons Guinea pigs Humans Certain rodents • Role of wildlife in RVF epidemiology not clear
  • 9. Has there been any changes in geographical range of the disease? 1950s – 1990s 2000 - 2015 2016- now
  • 10. Drivers • 2000, following heavy rainfall • About 2000 humans infected, 245 deaths • Thousands of sheep and goats affected • RVF virus introduction linked to livestock trade • Evidence of new transmissions 2004 • C. tritaeniorhynchus, A. vexans arabiensis • 1987, 93, 98, 2003 • Heavy rainfall, following a short rainless period • Ae. aegypti, C. nebulosus, A. gambiae, C. quinquefasciatus • Mar 1990 and Jan 2008 • Livestock movement from Comoros • Climate variables not clear • 1977 outbreak • Suspected to be due to livestock movement or wind-assisted migration of mosquitoes • Heavy, persistent rainfall
  • 11. Potential interventions • Livestock vaccination – key intervention • Challenges: – Vaccine safety concerns Vaccine Source Challenges Smithburn Isolated from mosquitoes in 1944 • Attenuated strain passaged in mice – associated with abortions and teratogenicity • Formalin inactivated – poor immunogenicity MP-12 Isolated from a patient in Egypt and subjected to serial passages Hepatocellular degeneration and necrosis Clone 13 Recovered from infected patient on Central Africa Crosses ovine placental barrier leading to foetal infections, malformations and stillbirths
  • 12. New vaccines • Development of new vaccines to address safety challenges – adenovirus-vectored vaccine for RVF called ChAdOx1-GnGc (Warimwe et al. 2013) – Vector -- replication-deficient chimpanzee adenovirus, ChAd – Clones being used code code RVFV Gn and GC envelop glycoproteins – Vaccine has passed safety tests but more on- farm trials being planned – Jenner Institute, Wellcome Trust-KEMRI, ILRI and KALRO
  • 13. Gaps in vaccination strategies • Current strategy – reactive vaccination which often fails to achieve required coverage • RVF vaccines often delivered through state financing – levels of acceptance variable • Activities: - Stakeholder engagements to design new vaccination strategies e.g. routine vaccination in the high risk areas - Studies to understand barriers to vaccination uptake – gender, knowledge, attitude and practices
  • 14. Technical studies to inform vaccination strategies 0 7 10 14 21 28 56 84 112 140 168 196 224 252 280 308 336 364  Serum  White blood cells in RNAlater  Serum Days post vaccination Smithburn RVF vaccine • Collect WBC at early time-points for transcriptomics • Collect sera at all time-points – cELISA – VNT • Study effects of concurrent infections
  • 15. Sub-county Vet Department Community Disease Reporter Syndromic surveillance National DVS County DVS •Types of drugs sold •Reported syndromes Agro-veterinary shops Abattoirs •No. slaughtered/day •Ante-mortem/PM lesions &parasites •Syndromes/rumours •Disease outbreaks Livestock owner Livestock markets •Syndromes •Disease outbreaks •Movement patterns
  • 17. • Gaps in surveillance: – Sustainability – Levels of knowledge – variable https://ilvac.net/2018/06/22/introducing-english-and- swahili-instructional-videos-on-the-patterns-signs- symptoms-and-control-of-rift-valley-fever/
  • 18. Statistical and mathematical modelling • A system/tool for forecasting risk and identifying hot spots for targeted intervention • Evaluate effectiveness of interventions • Analyse climate change impacts
  • 19. Species Total pop High risk (%) Camels 1,054,319 37% Goats 12,800,000 25% Sheep 9,941,564 22% Cattle 12,400,000 27% RVF risk SD (RVF risk) Sheep Cattle Goats Camels Robinson TP, et al. Mapping the global distribution of livestock. PLoS One. 2014;9. doi:10.1371/journal.pone.0096084
  • 20. Climate change Current distribution Predicted distribution In 2050 - RCP 4.5 Predicted distribution In 2050 - RCP 8.5
  • 21. Concluding remarks • RVF risk likely to intensify in some locations – more studies to predict future occurrence patterns • Strategies for deployment of interventions – this has attracted limited attention • Co-occurrence with other viruses – e.g. Ngari virus • Work more with policy makers to improve effectiveness of response
  • 22. Acknowledgements Department of Veterinary Services Kenya Medical Research Institute University of Nairobi Bura Irrigation Scheme
  • 23. better lives through livestock ilri.org This presentation is licensed for use under the Creative Commons Attribution 4.0 International Licence.