Global Health: the Zimbabwe and Haiti Cholera Epidemics

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Global Healththe Zimbabwe and Haiti Cholera
Epidemics

• J. Glenn Morris, Jr., MD, MPHTM
• UF Emerging Pathogens Institute

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Amount and patterns of disease burden in 3 major
world regions
Population 2.3 2.4 1.3 (billions)
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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, SH
Indoor smoke from solid fuels
Developing high mortality
Developing lower mortality
Iron deficiency
Developed
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
7
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Attributable mortality in millions (Total 55.9
million)
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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 Mans Burden

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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

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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

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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

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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
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Cholera Transmission Pathways
Spatio-Temporal Heterogeneity
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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 5.9
2000 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
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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

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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.
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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

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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
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Epidemic Spread from Bietbridge and Harare
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R0 by Province
  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)
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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)

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Vaccination Coverage Required to drop R0 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
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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

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Haiti Earthquake, January 12, 2010
Almost total destruction of public health
infrastructure, including water and sewerage
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PHHP/IFAS Long-term Focus on Development of
Sustainable Community
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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

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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 gt1,000 copies of instructions for
  ORS in Creole
• Outbreak assessment
• Assessment of clonality
• Application of mathematical models

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VNTR loci vary by the number of repeated units
Repeating unit is the hexamer AACAGC
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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.
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Mapping R0 values
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Haiti Estimates 10/31-11/29/2010
Department 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
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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

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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