SingaporeWHO Health Forum

1
Modeling of Dengue TransmissionRole of
Transmission Thresholds, the Pupal Demographic
Survey, Targeted Source Reduction, and the
Utility of El Niño Southern Oscillation Forecasts

• Singapore-WHO Health Forum
• Environmental Dimensions and Policies for Dengue
  Prevention and Control
• 22-25 October 2001
• Dana A. Focks
• Temporary Advisor for WHO

2
Outline of topics to be covered

• Simulation models
• Pupal and demographic survey vs. traditional
  Stegomyia indices
• Transmission thresholds and risk assessment
• Targeted source reduction
• Early-warning system based on El Niño Southern
  Oscillation (ENSO) forecasts and sea surface
  temperature (SST) anomalies
• Materials available at www.ID-Analysis.com

3
Simulation models- characteristics

• Mechanistic, first principals, life history
• Site-specific requiring information on
• Types, numbers, productivity of breeding
  containers
• Daily rainfall and temperature
• Demographic information- age-specific birth,
  death, and seroprevalence rates
• Available in DOS and Windows versions
• Web page on models, survey methods, etc.,
  available
• DOS versions available
• This PowerPoint at www.ID-Analysis.com

4
Simulation models- applications

• Studies on the impact of climate change
• Basic research
• Biting behavior of Ae. aegypti- Thailand, NIH
• Influence of endemic filariasis- NIH
• Impact of El Niño Southern Oscillation events-
  Indonesia Vi?t Nam
• Applied studies
• Entomological assumptions of dengue control-
  Peru, NIH
• Development of transmission thresholds
• Optimization of control programs
• Teaching and training

5
Simulation models- CIMSiM
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Simulation models- DENSiM
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Pupal and demographic survey

• Comparison of 3 traditional Stegomyia indices and
  an absolute density measure- pupae per person

• Note-
• No correlation between traditional indices and
  risk
• Risk varies spatially at scales of neighborhood,
  town, and country

8
Pupal and demographic survey
Pupae per person, hence risk, varies on multiple
scales- shown here at the neighborhood level
The Mynas neighborhood in Iquitos, Peru
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Pupal and demographic survey

• Modification and extension of the traditional
  survey method of counting larvae-positive
  containers for risk assessment and directing
  control efforts
• The survey method
• All water-holding containers are examined for the
  presence of pupae, data recorded by type of
  container
• Number of people residing at house recorded
• Need to survey ca. 50 houses to obtain useful
  information
• Provides estimates by type of container of
• pupae / container- important for targeted source
  reduction
• pupae / person- essential for risk assessment,
  thresholds
• Also provides estimates of traditional indices

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Transmission thresholds and risk assessment

• What is the relationship between survey results
  and risk? There are a number of factors
• Pupae per person
• Seroprevalence of antibody
• Circulating viruses
• Temperature
• Host availability
• Control efforts

Entomologic factors
Serologic factors
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Transmission thresholds and risk assessment

• Two approaches have been used to relate risk as a
  function of temperature, pupae per person, and
  seroprevalence
• Initial method Parameterize CIMSiM/DENSiM and
  evaluate- difficult
• Current method Use a simple table of
  transmission thresholds- easy

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Transmission thresholds and risk assessment

• Thresholds based on two well-known concepts
• The Mass Action Principal- the course of an
  epidemic is dependent on the rate of contact
  between susceptible hosts and infectious vectors
• Threshold Theory- the introduction of a few
  infectious individuals into a community of
  susceptibles will not give rise to an outbreak
  unless the density of vectors exceeds a certain
  critical level

Focks, D. A., R. J. Brenner, J. Hayes, E.
Daniels. 2000. Transmission thresholds for dengue
in terms of Aedes aegypti pupae per person with
discussion of their utility in source reduction
efforts. Am J Trop Med Hyg. 62 11-18.
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Transmission thresholds- development

• Gonotrophic development rate (table) and daily
  survival estimated with CIMSiM

Temp (oC) Rate (da-1)
Weight (mg) 22 .165 .233 24 .199
.232 26 .239 .233 28 .287 .236 30
.344 .244 32 .411 .275 Adult survival
independent of temperature- 0.89 / day
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Transmission thresholds- development

• Survivals, egg hatch, and the possibility of
  adult populations as a function of temperature

Temp (oC) Population Sadult Segg S larval
S pupal Egg hatch 20 -
89 97 99 99 - 22
89 92 99 99 24
89 88 99 99 26
89 84 99 99 28
89 78-80 99 99 30
89 68-72 99 99
32 89 58-62 99 99
34 89 52-55 99 99
36 - 81 46-49 99 99
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Transmission thresholds- development

• The pupal development period, expected daily
  number of newly-emerged females, and associated
  standing crop of females of all ages for a
  standing crop of 100 Ae. aegypti pupae

Temp Days Number of adult
females Ratios of standing crops
New Standing crop Pupae/female
Females/pupa 22 4.06 10.2 88
1.14 0.88 24 3.33 12.5 107
0.94 1.07 26 2.66 15.6 134
0.75 1.34 28 2.04 20.4 175
0.57 1.75 30 1.46 28.4 244
0.41 2.44 32 0.92 45.2 388
0.26 3.88
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Transmission thresholds- development

• Incubation period of the virus in the mosquito
  (EIP), a non-linear function of temperature,
  influences the proportion of females with virus
  and strongly influences transmission potential

initial blood meal with virus
proportion infected at high temp
infected at low temp
EIPwarm
EIPcool
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Transmission thresholds- the table

• Transmission thresholds by temperature and
  initial seroprevalence a

Temp C Initial seroprevalence of
antibody 0 33 67 22 7.13 10.7 23.
3 24 2.20 3.47 7.11
26 1.05 1.55 3.41 28 0.42 0.61 1.27
30 0.10 0.15 0.30 32 0.06 0.09 0.16
a assuming 12 monthly introductions of a single
viremic individual
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Transmission thresholds- as a function of the
magnitude of viral introduction

• Thresholds at 28oC for single (one-time)
  introductions of 1, 2, 4, or 8 viremic
  individuals, and 12 monthly introductions of a
  single viremic person as a function of initial
  seroprevalence

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Transmission thresholds- observed pupae per
person

• Observed average numbers of Ae. aegypti pupae
  per person in various dengue-endemic or
  dengue-receptive locations

Location Average annual temp
Pupae per person Reynosa, Mexico 23.0
2.8 Mayaguez, Puerto Rico 25.9
1.7 Yogyakarta, Indonesia 26.3
0.5 Trinidad (20 sites) 27.0 22.7 a San
Juan, Puerto Rico 27.3 2.8 Bangkok,
Thailand 28.7 1.7 a range 1.4
63.4
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Targeted source reduction

• History of dengue control methods
• Insecticides
• Eradication
• On-going source reduction
• Combinations

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Targeted source reduction

• See spreadsheet- Worksheet to targeted
  reductions- S Viet Nam.xls

www.ID-Analysis.com
22
Targeted source reduction- the importance of
especially productive breeding containers

• Distribution of the number of pupae/container is
  not normally distributed, but clumped
• In some locations, less than 1 of containers
  produce gt95 of the adults
• Rare containers account for essentially all
  production in some areas examined
• Iquitos, Peru
• Northern Mexico and southern Texas
• San Juan and Mayaguez, Puerto Rico
• Yogyakarta, Indonesia- an exception!
• In some communities, productive containers can be
  found quickly by their characteristics- outdoors,
  abandoned, under vegetation, etc.
• Control based on controlling rare but productive
  containers
• Cheaper than insecticides and traditional source
  reduction
• Could be initiated in response to epidemic or
  ENSO forecast
• Manuscript in preparation

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Early warning systems- based on SST, lagged
cases, weather
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Proposed early warning and control system for
Viet Nam

• The National Programme for the Control of Dengue
  Fever/Dengue Haemorrhagic Fever

• Preventing DHF epidemics elimination of
  DHF-related mortality
• Reducing DF/DHF morbidity of a level where it
  is no longer a major public health problem
• Confirming the clinical diagnosis of dengue in
  10 of cases in selected provinces and identify
  the serotypes involved
• Control methods are community-based involving
  the integrated use of insecticides, biologicals,
  source reduction, and education

Chief architects of the National Programme Dr.
Vu Sin Nam, Chief Entomologist, National
Institute of Hygiene and Epidemiology, Ha
Noi Dr. Nguyen Thi Kim Tien, Deputy Director,
Pasteur Institute and Chief of Planning
Department for Research, Training, and
Co-operation, Ho Chi Minh City
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Proposed early warning and control system for
Viet Nam

• Similar trends observed in neighboring countries
  of Cambodia, Myanmar, Laos, Thailand, and
  Indonesia
• Trends reflect the interaction of many
  factors--herd immunity, virus types circulating,
  etc.
• Trends also reflect, to a significant degree, the
  weather anomalies associated with El Niño
  Southern Oscillation events

Dengue in Viet Nam
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Proposed early warning and control system for
Viet Nam
El Niño Southern Oscillation Weather anomalies
and prediction using sea surface temperatures and
models

• ENSO is associated with epidemiologically
  significant temperature and precipitation
  anomalies in the region of Viet Nam
• These anomalies are clearly and significantly
  (statistically, and from a practical stand point)
  associated with corresponding anomalies in dengue
  activity
• The region of Viet Nam has a strong ENSO-related
  temperature signal as seen in comparisons of
  regional-scale surface air temperature (SAT) for
  the region with sea surface temperature (SST)
• The SAT record lags the SST record slightly
  meaning that satellite-observed SST can be used
  to predict weather anomalies 3 months in advance
• Atmospheric models provide somewhat less reliable
  forecasts, but with greater lead times 6 to 9
  months

Who is El Niño anyway?. . And why cant we kill
him?
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Proposed early warning and control system for
Viet Nam

• Goal of proposed effort is to strengthen the
  National Programme by introducing in a
  sustainable fashion new tools involving
• Pupal and demographic survey permitting targeted
  source reduction and biocontrol using Mesocyclops
  Micronecta on a spatial basis
• Development of a GIS-based risk map system
  displaying, at the district level, estimates of
  pupae/person and transmission thresholds as a
  function of herd immunity, historical weather and
  ENSO forecasts

28
Proposed early warning and control system for
Viet Nam
Results of a hypothetical pupal and demographic
survey indicating the numbers and types of
containers per hectare, their associated average
standing crop of Ae. aegypti pupae, and the
contributions each makes toward the transmission
threshold as a function of temperature.
Temperature anomalies associated with ENSO state
are lower and higher than normal for La Niña and
El Niño, respectively.
1 The numbers in parentheses refer to the
thresholds associated with the historical
temperature anomalies associated with ENSO state.
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Proposed early warning and control system for
Viet Nam
Development of an ENSO-based risk map-

• Climate work- develop for each province
  estimates of
• Normal monthly weather and
• Departures from normal as a function of ENSO
  state for each month
• Entomological surveys-
• NIHE and Pasteur conduct detailed pupal
  demographic surveys in representative areas
• obtain estimates of average pupae/container by
  type of container
• Identify especially productive types of
  containers
• Collaborator system supplies counts of containers
  by type
• Risk assessment- Estimate pupae/person using 1)
  collaborator data on numbers and types of
  containers combined with 2) NIHE/Pasteur data on
  pupae/container

30
Proposed early warning and control system for
Viet Nam
Development of an ENSO-based risk map, contd-

• Develop GIS systems- National Institute of
  Hygiene and Epidemiology and Pasteur Institute to
  display by district and month
• Observed pupae/person
• Current and projected transmission thresholds
• Results of active surveillance- virologic,
  serologic, case reports
• GIS systems highlight-
• Current risk maps of the ratio of observed
  pupae/person to thresholds
• Risk maps of anticipated conditions as a function
  of predicted ENSO state or SST anomalies
• Results- Effort allows evaluating/estimating a
  number of critical elements
• Degree of suppression required
• Guidance on targeting intervention efforts
• Ability to evaluate efforts
• Early warning of epidemic conditions

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References

• Focks DA, Haile DG, Daniels E, Mount GA, 1993.
  Dynamic life table model for Aedes aegypti (L.)
  (Diptera Culicidae). Analysis of the literature
  and model development. J Med Entomol 30
  1003-1017.
• Focks DA, Haile DG, Daniels E, Mount GA, 1993.
  Dynamic life table model for Aedes aegypti (L.)
  (Diptera Culicidae). Simulation results and
  validation. J Med Entomol 30 1018-1028.
• Focks DA, Daniels E, Haile DG, Keesling JE, 1995.
  A simulation model of the epidemiology of urban
  dengue fever Literature analysis, model
  development, preliminary validation, and samples
  of simulation results. Am J Trop Med Hyg 53
  489-506.
• Focks DA, Chadee DD. 1997. Pupal survey An
  epidemiologically significant surveillance method
  for Aedes aegypti An example using data from
  Trinidad. Am J Trop Med Hyg 56 159-167.
• Jetten TH, Focks DA. 1997. Changes in the
  distribution of dengue transmission under climate
  warming scenarios. Am J Trop Med Hyg 57
  285-297.
• Martens WJM, Jetten TH, Focks DA. 1997.
  Sensitivity of malaria, schistosomiasis and
  dengue to global warming. Climate Change 35
  145-156.
• Patz JA, Martens WJM, Focks DA, Jetten TH. 1998.
  Dengue fever epidemic potential as projected by
  general circulation models of global climate
  change. Environ Hlth Perspectives 106 147-152.
• Focks DA, Brenner RJ, Chadee DD, Trosper J. 1998.
  The use of spatial analysis in the control and
  risk assessment of vector-borne diseases. Am
  Entomologist 45 173-183.
• Focks DA, Brenner RA, Daniels E, Hayes J. 2000.
  Transmission thresholds for dengue in terms of
  Aedes aegypti pupae per person with discussion of
  their utility in source reduction efforts. Am J
  Trop Med Hyg. 62 11-18.
• Burke, D., A. Carmichael, D. Focks, D. Grimes, J.
  Harte, S. Lele, P. Martens, J. Mayer, L. Means,
  R. Pulwarty, L. Real, C. Ropelewski, J. Rose, R.
  Shope, J. Simpson, M. Wilson. 2001. Under the
  Weather Exploring the Linkages Between Climate,
  Ecosystems, Infectious Disease, and Human
  Health. National Research Council, National
  Academy Press, Washington, D.C.
• Focks DA, Patz, JA, Oman CS, Hayes J, Brenner RJ,
  Mearns LO, Kittel TGF, Rawlings J. 2001.
  Projections and analysis of the consequences of
  climate change on dengue transmission in southern
  Texas and northern Mexico. Environ Hlth
  Perspectives. (ms in preparation).
• Focks DA, Lele S, Brenner RJ, Scott TW, Morrison
  A. 2001. A potential dengue control strategy
  focusing on rare but extremely productive
  breeding containers. Bull WHO. (ms in
  preparation).
• Weidhaas DE, Focks DA. 2000. Disease control
  by vector management. In Edman, J. D. and B. F.
  Eldridge (eds) Textbook of Medical Entomology.
  Chapman and Hall. New York. 576 pp. (Book
  Chapter).