www.sciencemag.orgSCIENCE VOL 324 15 MAY 2009 Download full-text
Republic of the Congo, DRC). During the first
month after the influx, almost 50,000 refugees
died; cholera was a major contributor (1).
From 1995 to 2005, the largest number of
cholera cases and outbreaks in Africa contin-
ued to be reported from this area of the DRC
(2). Renewed fighting has displaced at least
250,000 people, making an already difficult
situation worse for more than a million people
living without clean water, food, or access to
health care. By December 2008, the most
recent cholera outbreak had affected 10,332
persons and resulted in 201 deaths (3).
Cholera is also in the headlines in Zimbabwe.
From August 2008 to February 2009, the
number of reported cases was 70,643 with
3467 deaths (4). Cholera is also spreading to
the neighboring countries of South Africa,
Mozambique, Zambia, and Angola (5–7).
The management of cholera outbreaks has
changed little over the last decades. Oral rehy-
dration solution (ORS) is accepted as the cor-
nerstone for rehydration, although for those
severely dehydrated, intravenous fluids are
n July 1994, 500,000 to 800,000 Rwandans
crossed the border into the North Kivu
region of Zaire (now called the Democratic
life-saving. Provision of safe water and ade-
quate sanitation can be established as emer-
gency measures but are not guaranteed to
remain once the outbreak ends.
The international community has responded
vigorously within recommended guidelines.
Physicians for Human Rights recently called
on the United Nations to take responsibility for
the Zimbabwean health system (6). The World
Health Organization’s (WHO’s) Global Task
Force on Cholera Control urged prioritization
of prevention, preparedness, and response
activities and an efficient surveillance system
(8). The WHO’s Disease Control in Humani-
tarian Emergencies program is helping with
distributing ORS and chlorine tablets, finding
funds to pay thousands of Zimbabwean health-
care workers, and providing better services in
remote areas (9). Although these efforts have
saved many lives, the rising cases and deaths
point to the limitations of the current strategy.
Is it time to consider other options? An oral
cholera vaccine was evaluated in Mozambique
5 years ago and showed ~90% protection
against cholera of life-threatening severity,
even in a population in whom a high percent-
age was infected by HIV (10). Internationally
licensed and available, the vaccine has also
been shown to confer herd protection against
cholera among unvaccinated neighbors of vac-
cinees (11). To date, the WHO has been reluc-
tant to consider vaccination as a strategy to
contain cholera in Zimbabwe “due to its two-
dose regimen, short shelf-life, high cost, and
need for cold chain distribution” (8). There are
certainly logistical complexities to administer-
ing a two-dose regimen in a setting as desper-
ate and chaotic as Zimbabwe, as well as strate-
gic choices to be made for how to target high-
risk groups for vaccination. Yet delivery of this
vaccine was feasible in three WHO-sponsored
community demonstration projects in rural
and urban sub-Saharan Africa (10, 12, 13).
Further complicating a recommendation to
vaccinate is the existing dogma that “with the
currently available internationally prequalified
vaccine, vaccination is not recommended in an
area where an outbreak has already started”
(14). However, this dogma is based on a single
analysis (15) that assumed that outbreaks are
self-limited and short-lived, in contrast to
cholera in Zimbabwe, which has been raging
since mid-2008. If the blockade against poten-
tial use of oral cholera vaccines could be lifted,
then public-health workers, ministries of
health, international organizations, and donor
groups could discuss how, when, and where
the vaccine could be deployed.The cost of the
only internationally licensed oral cholera
vaccine (Dukoral,Crucell-SBL) is U.S. $7 to
$12 (€5.25 to €9) per dose; a lower price is
offered for WHO-supported programs. A
potentially cheaper vaccine was developed
in Vietnam; its technology was transferred
to Shanta Biotechnics (India) and is in clini-
cal trials (16, 17).In the short term, the vacci-
nation costs may be borne by donor founda-
tions and international organizations.
The size and expected duration of the out-
break would seem to justify the implementa-
tion of mass vaccinations. The lack of flexibil-
ity to adapt to the circumstances is regrettable;
for the people at risk it is a disaster.
References and Notes
1. Goma Epidemiology Group, Lancet 345, 339 (1995).
2. D. C. Griffith et al., Am. J. Trop. Med. Hyg. 75, 973 (2006).
3. F. Fleck, Bull. World Health Organ. 87, 6 (2009).
4. “Zimbabwe: Daily cholera update and alerts, 09 Feb
2009” (Government of Zimbabwe and WHO, Geneva,
5. National Outbreak Committee, Cholera Outbreak in South
Africa, National Outbreak Committee Situational Report
(Government of South Africa, Pretoria, 5 February 2009).
6. C. Kapp, Lancet 373, 447 (2009).
7. ProMED-mail, International Society for Infectious Diseases,
Brookline, MA, 7 February 2009; www.promedmail.org.
8. “An old enemy returns,” Bull. World Health Organ. 87,
9. R. Koenig, Science 323, 860 (2009).
10. M. E. S. Lucas et al., N. Engl. J. Med. 352, 757 (2005).
11. M. Ali et al., Lancet 366, 44(2005).
12. D. Legros et al., Bull. World Health Organ.77, 837 (1999).
13. C.-L. Chaignat et al., Expert Rev. Vaccines 7, 431 (2008).
14. WHO Global Task Force on Cholera Control, Cairo, Egypt,
14 to 16 December 2005 (WHO/CDS/NTD/IDM/2006.2,
WHO, Geneva, 2006).
15. A. Naficy et al., JAMA 279, 521 (1998).
16. D. Mahalanabis et al., PLoS One 3, e2323 (2008).
17. Clinical trials, http://clinicaltrials.gov/ct2/show/
18. J.C., J.L.D., and L.v.S. received support from the Bill and
Melinda Gates Foundation. R.B., J.C., G.D., R.G., M.G.,
I.G., J.H., M.A.L., I.L., R.N., G.J.V.N., P.O., F.S., P.H.L.,
and A.M.S. are/have been members of the Board of
Trustees and/or Scientific Advisory Group of IVI, which is
engaged in the development and technology transfer of
the oral vaccine described (17).
Long-lasting cholera outbreaks in Africa
suggest limitations in the current strategy
of disease control.
The Cholera Crisis in Africa
S. Bhattacharya,1R. Black,2L. Bourgeois,3J. Clemens,4 A. Cravioto,5J. L. Deen,5*
Gordon Dougan,6R. Glass,7R. F. Grais,8M. Greco,9I. Gust,10J. Holmgren,11S. Kariuki,12
P.-H. Lambert,13M. A. Liu,14I. Longini,15G. B. Nair,16R. Norrby,17G. J. V. Nossal,10P. Ogra,18
P. Sansonetti,19L. von Seidlein,5F. Songane,20A.-M. Svennerholm,11D. Steele,3R. Walker3
1Indian Council of Medical Research, Ansari Nagore, New
Delhi, 110029, India. 2Department of International Health,
Bloomberg School of Public Health, Johns Hopkins University,
Baltimore, MD 21205, USA. 3Enteric Vaccine Initiative, PATH,
Seattle, WA 98107, USA. 4International Vaccine Institute,
Seoul, 151-600, Korea. 5Centre for Diarrhoeal Disease
Research, Dhaka 1000, Bangladesh. 6The Wellcome Trust
Sanger Institute, Wellcome Trust Genome Campus, Hinxton,
Cambridge, CB10 1RQ, UK. 7Fogarty Institute, National
Institutes of Health, Bethesda, MD 20892, USA. 8Epidemi-
ology and Population Health, Epicentre, FR-75011 Paris,
France. 9FR-69110 Lyon, France. 10The Department of Micro-
biology and Immunology and the Department of Pathology,
University of Melbourne, Melbourne, VIC, 3010, Australia.
11University of Gothenburg, SE-405 30 Gothenburg, Sweden.
12Centre for Microbiology Research, Kenya Medical Research
Institute, Nairobi, Kenya. 13University of Geneva, CH-1211
Geneva 4, Switzerland. 14Karolinska Institute, SE-171 77
Stockholm, Sweden. 15Fred Hutchinson Cancer Research
Center and the University of Washington, Seattle, WA98109,
USA. 16National Institute of Cholera and Infectious Disease,
Kolkata, 700010, India. 17Swedish Institute for Infectious
Disease Control, SE-171 82 Solna, Sweden. 18University at
Buffalo, School of Medicine and Biomedical Sciences,
Buffalo, NY14214, USA. 19Unité de Pathogénie Microbienne
Moléculaire, INSERM U786, Institut Pasteur, FR-75724 Paris
Cedex 15, France.20Partnership for Maternal, Newborn and
Child Health, 1211 Geneva, Switzerland.
*Author for correspondence. E-mail: firstname.lastname@example.org
Published by AAAS
on May 15, 2009