Transcript No Slide Title

Global Health:
the Zimbabwe and Haiti
Cholera Epidemics
J. Glenn Morris, Jr., MD, MPH&TM
UF Emerging Pathogens Institute
Amount and patterns of disease burden in
3 major world regions
900
Unintentional injury
800
Intentional injury
Group III - Injuries
Other non-communicable
700
DALYs (000,000s)
Neuro-psychiatric
600
Chronic respiratory
500
Cancer
Vascular
400
Nutritional
300
Maternal and perinatal
200
Respiratory infections
Infectious and parasitic diseases
100
0
Population
(billions)
Group II Noncommunicable
conditions
Developing –
high mortality
2.3
Developing –
lower mortality
2.4
Developed
1.3
Group 1 - Communicable
diseases, maternal and
perinatal conditions and
nutritional deficiencies
Global distribution of mortality attributable to 20
leading selected risk factors
High blood pressure
Tobacco
High cholesterol
Underweight
Unsafe sex
Low fruit and vegetables
High BMI
Physical inactivity
Alcohol
Unsafe water, S&H
Indoor smoke from solid fuels
Developing high mortality
Developing lower mortality
Developed
Iron deficiency
Urban air pollution
Zinc deficiency
Vitamin A deficiency
Unsafe health care injections
Occupational particulates
Occupational injury
Lead exposure
Illicit drugs
0
1
2
3
4
5
6
Attributable mortality in millions (Total 55.9 million)
7
8
Global Health
• Issues that impact global health
– Increasing income differentials among countries that foster
poverty-associated conditions for poor health
– Variance in environmental and occupational health and safety
standards that contribute to dangerous working conditions
– Global environmental change leading to such things as
depletion of freshwater supplies and the loss of arable lands
– Re-emergence of infectious diseases
• Defining the role of the Developed World
– Easterly: “The White Man’s Burden”
The Critical Importance of Sustainability
Give a man a fish and you feed him for a day. Teach
a man to fish and you feed him for a lifetime.
Chinese Proverb
Lunchtime Global Health Talks
(Courtesy of the Hispanic American Medical Student Association [HAMSA], the Emerging
Pathogens Institute, and the Department of Environmental and Global Health, PHHP)
• January 4, Dr. Glenn Morris
– Global Health: the Zimbabwe and Haiti Cholera
Epidemics
• February 8, Dr. Mike Lauzardo
– Mexico – Our most important partner in global health
• March 29, Dr. Charles Hobson
• April 19, Dr. Greg Gray
– Opportunities for health professionals in global health
Cholera and
Cholera Toxin
• Action
– Constitutive activation of adenylate cyclase by A1 subunit,
through G protein, probably for life of cell
– Results in increased intracellular cAMP concentrations, leading
to increased Cl- secretion by intestinal crypt cells and decreased
NaCl coupled absorption by villus cells
– Net movement of electrolytes results in water flow into the
lumen of the intestine
– Does NOT affect glucose-mediated transport
“The discovery that sodium transport and glucose transport are coupled in the small
intestine, so that glucose accelerates absorption of solute and water, was potentially
the most important medical advance this century.”
Lancet, 1978
Cholera Transmission Pathways
Environmental
Parameters
V. cholerae in
environment
including
plankton
Cholera
infections in
humans
Spatio-Temporal
Heterogeneity
Deaths CFR %
57
2.8
323
6
0
0
0
0
0
0
0
0
46
5.2
240
5.9
71
3.7
13
2
354
9.6
19
2.2
10
8
15
6.5
63
8
4
6.2
1596
5
2667
4
70000
12.0
Cholera Cases
60000
Cholera Deaths
10.0
CFR%
50000
8.0
40000
6.0
30000
4.0
20000
2.0
10000
0
0.0
Time (years)
Cholera cases and deaths, Zimbabwe, 1992-2009
CFR%
Cases
2048
5385
3
0
0
1
883
4081
1911
649
3684
879
125
231
789
65
31921
66664
Cholera cases/deaths
Year
1992
1993
1994
1995
1996
1997
1998
1999
2000
2001
2002
2003
2004
2005
2006
2007
2008
2009
Why did the Zimbabwe Epidemic Occur?
• Major driver: breakdown of public health
infrastructure/water and sewerage systems
• Other factors?
– Pattern of spatial spread
– Contribution of human direct vs. environmental
transmission
– Potential impact of vaccination
Legend
Harare (H)
Bulawayo(B)
Mashonaland Central (MC)
Mashonaland East (ME)
Mashonaland West (MW)
Midlands (MD)
Manicaland (ML)
Matebeleland South (MS)
Matebeleland North (MN)
Masvingo (MV)
Map of Zimbabwe, provinces and neighboring countries. The red colored
regions show one of the cholera affected districts (Manica) in Mozambique in
2006 and some of the cholera affected provinces (Southern and Lusaka) in
Zambia in 2010 which are on the border with Zimbabwe.
Zimbabwe
• Spatial Models
• SIR model
– Calculation of R0
• Average number of secondary infections that occur when
one infective is introduced into a completely susceptible
host population
– Estimation of relative contributions of:
• human/human transmission (short cycle, increased
infectivity) vs.
• human/environment/human (long cycle, decreased
infectivity)
– Use of these estimates to assess utility of
intervention strategies
Case Clusters, Weeks 1-5
First cases:
Karibe district (on border with
Zambia): peak weeks 1-2
Major initial epidemics:
Beitbridge (on South African
border): peak weeks 2-3
Harare (capital): peak weeks
4-5
Spread to district centers
? Importance of funeral
celebrations
Epidemic Spread from
Bietbridge and Harare
Time of peak of the outbreak
(Weeks)
Time of peak of the outbreak
(Weeks)
20
16
14
12
10
8
6
4
2
0
18
16
14
12
10
8
6
4
2
0
0
0.5
1
1.5
Distance from Bietbridge ( X 111 km)
0
0.5
1
1.5
Distance from Harare (X 111km)
ℛ0
95 % CI
Harare
1.52
(1.14-1.96)
Bulawayo
1.36
(1.12-1.61)
Mashonaland
Central
1.38
(1.21-1.54)
Mashonaland
East
1.11
(0.90-1.32)
Mashonaland
West
1.87
(1.34-2.38)
Midlands
1.39
(1.23-1.56)
Manicaland
2.06
(1.78-2.34)
Matebeleland
South
2.72
(1.19-4.24)
Matebeleland
North
1.72
(1.44-1.99)
Masvingo
1.61
(1.20-2.03)
Zimbabwe
1.15
(1.08-1.23)
R0 by Province
Relative Contribution of “Human”
vs. “Environmental” Source
• Zimbabwe
– RE (long cycle) = 0.20
(95% CI: 0.15-0.2); 17%
– RH (short cycle) = 0.95
(95% CI: 0.93-0.98); 83%
– R0 = 1.15
(95% CI: 1.08-1.23)
Vaccination Coverage Required to drop
R0 below 1
Harare
Bulawayo
Mashonaland
Central
44%
34%
Mashonaland East
13%
Mashonaland West
59%
Midlands
Manicaland
36%
66%
Matebeleland South
81%
Matebeleland North
53%
Masvingo
Zimbabwe
49%
17%
35%
Summary - Zimbabwe
• Stepwise spread of illness from key urban centers into districts
• R0 varied by province, indicative of differences in transmission
dynamics
– Values of R0 were in range of 1.11-2.72
– Major contribution from human/human (short cycle) transmission – but
both modes of transmission necessary to maintain epidemic
– While there was wide variation in needed vaccination coverage, based on
R0, data provide insight into how transmission could be stopped
Key contribution: Understanding of transmission dynamics, and
approaches to vaccine use, that can guide interventions of
Ministry of Health
Haiti: Earthquake, January 12, 2010
Almost total
destruction of
public health
infrastructure,
including water
and sewerage
PHHP/IFAS: Long-term Focus on
Development of Sustainable Community
Cholera: October 21, 2010
• While destruction of public health
infrastructure made Haiti “high
risk” for cholera, no cases present
in the country since 1960
• First cases – along Artibonite
River
– Association of cases with river
– PFGE – isolates clonal
– UN unit from Nepal at epicenter of
outbreak
• Rapid subsequent spread
throughout country
UF Involvement in Cholera Outbreak
• Focus on sustainability, data
collection to guide subsequent
interventions
• Oral rehydration
– Preparation of 2,000 ORS packets
by Pharmacy students
– Distribution of >1,000 copies of
instructions for ORS in Creole
• Outbreak assessment
– Assessment of clonality
– Application of mathematical models
VNTR loci vary by the number of
repeated units
Repeating unit is the hexamer AACAGC
Distribution of Vibrio cholerae VNTR sequence types among 190 V.
cholerae isolates from 13 Haitian patients with severe diarrhea. Numbers
represent number of repeats for the four alleles tested: VC0147, VC0437,
VC1650, and VCA0171, respectively. A is the dominant sequence type,
identified in 12 of 13 patients for whom VNTR data were available; B, C,
and D were each present in one patient, with patients having type B or type
C also having type A.
Mapping R0 values
Haiti Estimates: 10/31-11/29/2010
Department
Population Size
R0
Vaccination Coverage(%)
Haiti [Country]
Artibonite
Centre
Grande Anse
Nippes
8089479
1.28
26
1091374
1.37
32
525253
1.72
49
677846
1.10
10
266379
0.0031
N/A [outbreak starting]
Nord
Nord Ouest
Nord Est
Ouest**
Ouest
Port-au-Prince
Sud
Sud Est
811467
1.44
36
459007
1.14
14
282903
1.91
56
897401
1.19
18
2811300
1.61
45
1913899
2.03
60
688024
1.16
16
475926
0.043
N/A [outbreak starting]
Ouest includes Ouest** and Port-au-Prince
Summary - Haiti
• Outbreak from apparent common source, with rapid spread
facilitated by total destruction of public health infrastructure
• R0 varied by province, indicative of differences in transmission
dynamics
– Values of R0 were in range of 1.1-2.03
– Effective vaccination coverage would require immunization of 10-56% of
population in various provinces
Key contributions
– Immediate provision of ORS, with concurrent education program
– Understanding of transmission dynamics, and approaches to vaccine use,
that can guide interventions of Ministry of Health
How do you do “Sustainability”?
• Provide means of facilitating long-term local efforts to
control disease
– Research
• Understanding of disease transmission pathways, new vaccines, new
drugs for neglected diseases
– Education
• Assist with development of sustainable public health
infrastructure
–
–
–
–
Water and sewerage systems
Nutrition programs
Vaccination programs
General education programs