global health: the zimbabwe and haiti cholera epidemics j. glenn morris, jr., md, mph&tm uf...
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Global Health:Global Health:the Zimbabwe and Haiti the Zimbabwe and Haiti
Cholera EpidemicsCholera Epidemics
J. Glenn Morris, Jr., MD, MPH&TMUF Emerging Pathogens Institute
Amount and patterns of disease burden in Amount and patterns of disease burden in 3 major world regions3 major world regions
0
100
200
300
400
500
600
700
800
900D
AL
Ys
(000
,000
s)Unintentional injury
Intentional injury
Other non-communicable
Neuro-psychiatric
Chronic respiratory
Cancer
Vascular
Nutritional
Maternal and perinatal
Respiratory infections
Infectious and parasitic diseases
Group 1 - Communicable diseases, maternal and perinatal conditions and nutritional deficiencies
Group II - Noncommunicable conditions
Group III - Injuries
Developing –high mortality
Developing –lower mortality
Developed
Population 2.3 2.4 1.3(billions)
Global distribution of mortality attributable to 20 Global distribution of mortality attributable to 20 leading selected risk factorsleading selected risk factors
0 1 2 3 4 5 6 7 8
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
Iron deficiency
Urban air pollution
Zinc deficiency
Vitamin A deficiency
Unsafe health care injections
Occupational particulates
Occupational injury
Lead exposure
Illicit drugs
Attributable mortality in millions (Total 55.9 million)
Developing high mortality
Developing lower mortality
Developed
Global HealthGlobal 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 SustainabilityThe 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 TalksLunchtime Global Health Talks(Courtesy of the Hispanic American Medical Student Association [HAMSA], the Emerging (Courtesy of the Hispanic American Medical Student Association [HAMSA], the Emerging Pathogens Institute, and the Department of Environmental and Global Health, PHHP)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 and Cholera ToxinCholera 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 PathwaysCholera Transmission Pathways
Cholera infections in humans
V. cholerae in environment
including plankton
Environmental Parameters
Spatio-Temporal Heterogeneity
Year Cases Deaths CFR %
1992 2048 57 2.8
1993 5385 323 6
1994 3 0 0
1995 0 0 0
1996 0 0 0
1997 1 0 0
1998 883 46 5.2
1999 4081 240 5.92000 1911 71 3.7
2001 649 13 2
2002 3684 354 9.6
2003 879 19 2.2
2004 125 10 8
2005 231 15 6.5
2006 789 63 8
2007 65 4 6.2
2008 31921 1596 5
2009 66664 2667 4
Cholera cases and deaths, Zimbabwe, 1992-2009
Why did the Zimbabwe Epidemic Occur?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
LegendHarare (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.
ZimbabweZimbabwe• 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 1-5Case Clusters, Weeks 1-5First 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 Epidemic Spread from Bietbridge and HarareBietbridge and Harare
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)
RR00 by Province by Province
Relative Contribution of Relative Contribution of ““HumanHuman”” vs. vs. ““EnvironmentalEnvironmental”” Source 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 Vaccination Coverage Required to drop RR00 below 1 below 1
Harare 44%Bulawayo 34%
Mashonaland Central
35%
Mashonaland East 13%
Mashonaland West 59%
Midlands 36%Manicaland 66%
Matebeleland South 81%
Matebeleland North 53%
Masvingo 49%
Zimbabwe 17%
Summary - ZimbabweSummary - 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, 2010Haiti: Earthquake, January 12, 2010Almost total destruction of public health infrastructure, including water and sewerage
PHHP/IFAS: Long-term Focus on PHHP/IFAS: Long-term Focus on Development of Sustainable Community Development of Sustainable Community
Cholera: October 21, 2010Cholera: 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 OutbreakUF 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 VNTR loci vary by the number of repeated unitsrepeated 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 RMapping R00 values values
Haiti Estimates: 10/31-11/29/2010Haiti Estimates: 10/31-11/29/2010Department Population Size R0 Vaccination Coverage(%)
Haiti [Country] 8089479 1.28 26
Artibonite 1091374 1.37 32
Centre 525253 1.72 49
Grande Anse 677846 1.10 10
Nippes 266379 0.0031 N/A [outbreak starting]
Nord 811467 1.44 36
Nord Ouest 459007 1.14 14
Nord Est 282903 1.91 56
Ouest** 897401 1.19 18
Ouest 2811300 1.61 45
Port-au-Prince 1913899 2.03 60
Sud 688024 1.16 16
Sud Est 475926 0.043 N/A [outbreak starting]
Ouest includes Ouest** and Port-au-Prince
Summary - HaitiSummary - 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 How do you do ““SustainabilitySustainability””??• 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
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