V. cholerae - Filippo Pacini
V. cholerae - Filippo Pacini
V. cholerae - Filippo Pacini
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Cholera in the AMERICAS: Peru 1991 and<br />
Haiti 2010, lessons for XXI century<br />
EDUARDO GOTUZZO, M.D. FACP,FIDSA<br />
Chief, Department of Infectious Diseases, Tropical Medicine and<br />
Dermatology - HOSPITAL NACIONAL CAYETANO HEREDIA<br />
Director, Institute of Tropical Medicine “Alexander von<br />
Humboldt” - UNIVERSIDAD PERUANA CAYETANO HEREDIA<br />
<br />
SIMPOSIUM FILIPPO PACINI.-PISTOIA JUNE 2012
EPIDEMIOLOGY<br />
THE AGENT<br />
PATHOPHYSIOLOGY<br />
CLINICAL PICTURE<br />
TREATMENT<br />
PREVENTION AND CONTROL<br />
RECENT EPIDEMICS
EPIDEMIOLOGY<br />
Transmission<br />
» fecal-oral route; foodborne and waterborne<br />
» person to person<br />
Reservoir<br />
» acquatic environments; free living cycle, non-culturable state<br />
» human reservoir<br />
Infectious dose; 10 2<br />
to 10 6<br />
Incubation period; 14h to 5 days<br />
Endemic vs. epidemic patterns<br />
Seasonality; warm seasons
EPIDEMIC AND ENDEMIC PATTERNS<br />
Feature Epidemic Endemic<br />
Age at greatest risk all ages.- children (2-15)<br />
mainly adults<br />
Transmission single route many routes<br />
Reservoir absent acquatic<br />
humans<br />
Asymptomatic infection less common more common<br />
Secondary spread high low<br />
Type of studies to evaluate risk factors<br />
case-control cohort studies
SEVEN PANDEMICS OF CHOLERA<br />
Pandemic Year Comments<br />
1 1817-23 Fisrt epidemic in the modern era<br />
2 1829-51 Herman in Russia conceived the idea of giving<br />
intravenous fluids<br />
O´Shaugnessy and Latta infused saline<br />
solutions to 15 patients; 5 survived<br />
3 1852-9 <strong>Filippo</strong> <strong>Pacini</strong> coined the name V. <strong>cholerae</strong><br />
John Snow; the role of water, 1855<br />
4 1863-79 Cholera was considered a moral problem<br />
5 1881-96 Koch identified the Kommabacillen, 1883<br />
6 1899-1926 Rogers reduced mortality with IV fluids<br />
7 1961 .... Cash reported the succesful use of ORS<br />
Greenough reported the utility of tetracycline in<br />
severe cholera
THE PANDEMICS OF CHOLERA<br />
Seventh Previous six<br />
Pandemic Pandemics<br />
Place of origin Celebes Islands India-Bangladesh<br />
Time to reach India 10 years immediately<br />
Biotype El Tor Classical<br />
Duration, y more than 40 12 (mean)<br />
Resistant strains common uncommon<br />
Asymptomatic common uncommon<br />
carriers
EPIDEMIOLOGICAL DIFFERENCES BETWEEN<br />
THE TWO BIOTYPES OF V. <strong>cholerae</strong> O1<br />
%<br />
100<br />
80<br />
60<br />
40<br />
20<br />
0<br />
El Tor Classical<br />
Asymptomatic<br />
Some<br />
dehydration<br />
Severe<br />
dehydration
LEADERS ACQUIRING CHOLERA<br />
• Peter Tchaikovsky<br />
• George Hegel<br />
• George Baron Cuvier<br />
• Duke of Wellington<br />
• Thomas Hodgking<br />
J. Inf. Dis. 1984, 6(6):802
LIFE CYCLE OF Vibrio <strong>cholerae</strong>
Vibrio <strong>cholerae</strong>
THE AGENT<br />
Vibrio <strong>cholerae</strong> is a Gram negative bacilli, facultatively<br />
anaerobic, motile and curved<br />
It grows in alkaline conditions (6
MODEL FOR THE TRANSMISSION OF CHOLERA FROM<br />
THE ENVIRONMENT TO HUMANS
Vibrio <strong>cholerae</strong> ON THE SURFACE OF A<br />
COPEPODE
PATHOPHYSIOLOGY<br />
V. <strong>cholerae</strong> O1 and O139 have one or more copies of<br />
the genes ctxA and ctxB that encode the cholera toxin<br />
the cholera toxin has 2 sub-units: A or active and B for<br />
binding to a specific receptor, ganglioside GM1<br />
the A sub-unit activates the adenylate cyclase enzyme<br />
increasing cAMP levels:<br />
» promotes secretion of chloride by crypt cells<br />
» blocks absorption of sodium and chloride by villus cells<br />
the role of other toxins is less clear; zone ocludens,<br />
shigella like toxin, accessory enterotoxin
ELECTROLYTE CONCENTRATIONS IN CHOLERA STOOLS<br />
AND COMMON SOLUTIONS USED FOR ITS TREATMENT<br />
Na + Cl - K + HCO3 -<br />
Cholera stool<br />
adults 130 100 20 44<br />
children Intravenous solutions<br />
100 90 33 30<br />
Ringer´s lactate 130 109 4 28*<br />
Dhaka solution 133 154 13 48<br />
Normal saline 154 154<br />
WHO ORS 75 65 20 10**<br />
Concentrations are in mmol/L, * lactate instead of bicarbonate, ** trisodium citrate
“ At Athens a man was seized with cholera. He<br />
vomited, and was purged and was in pain, and<br />
neither the vomiting nor the purging could be<br />
stopped; and his voice failed him, and he could<br />
not be moved from his bed, and his eyes were<br />
dark and hollow, and spasms from the stomach<br />
held him, and hiccup from the bowels. He was<br />
forced to drink, and the two (vomiting and<br />
purging) were stopped, but he became cold “<br />
HIPPOCRATES
STOOL SAMPLE OF A CHOLERA PATIENT<br />
rice watery diarrhea with a fishy odour
A CHOLERA PATIENT FROM DHAKA, ICDDR,B
STOOL SAMPLE OF A CHOLERA PATIENT
Number of cases x 1000<br />
500<br />
400<br />
300<br />
200<br />
100<br />
0<br />
NUMBER OF CHOLERA CASES REPORTED<br />
TO WHO, 1984-2005<br />
1984 1985 1986 1987 1988 1989 1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005<br />
Asia Africa America<br />
Weekly Epidemiological Record 2006;81:297-308.
FOODBORNE TRANSMISSION<br />
Country of origin Year Implicated food<br />
Italy 1973 Raw shellfish (mussels)<br />
Portugal USA<br />
1974 Raw shellfish (cockles)<br />
Louisiana 1978 Cooked crabs<br />
Texas 1981 Cooked rice<br />
Colorado 1988 Raw oysters<br />
Imported, Ecuador 1991 Cooked crabs in salad<br />
Imported, Peru 1991 Shrimp and fish in salad<br />
Peru 1991 Cooked leftover rice<br />
cebiche, eating at street<br />
vendors
CLINICAL FINDINGS BY DEGREE OF DEHYDRATION<br />
Some<br />
Severe<br />
Loss of body weight 5-9% > 9%<br />
Mentation Radial pulse<br />
alert-restless drowsy, coma<br />
rate normal-rapid very rapid<br />
intensity weak feeble<br />
Respiration normal-deep deep-rapid<br />
Skin elasticity normal retracts slowly<br />
Eyes normal very sunken<br />
Voice normal-hoarse not audible<br />
Urine production normal oliguria
SITUATION OF PERU DURING 1991<br />
• Hyperinflation around 2 million per cent<br />
• Crowding of the population along big cities; terrorism<br />
• Unemployment<br />
• Lack of sanitation and water supply<br />
• El Niño
WATER SUPPLY AND SANITATION<br />
• International drinking water and sanitation decade<br />
» the goal was to extend and upgrade municipal and<br />
village water and sanitation in Latin America in the 80s<br />
» public water sources in 88% of urban cities and 55% of<br />
rural villages during 1988<br />
» 49% of urban populations were served by sanitary<br />
sewerage systems before 1990<br />
• Intermitent water delivery, suction in water lines<br />
• 75% of water systems did not treat water properly<br />
• less than 10% of all sewage was treated correctly
THE CHOLERA EPIDEMIC IN PERU<br />
The epidemic started simultaneously in three distant cities<br />
along the coast, during the third week of January 1991<br />
In less than three months all major cities reported cases<br />
Very high attack rates, but low case fatality rates<br />
High case fatality rates in rural areas of the jungle<br />
More than 25000 cases per week in 1991<br />
Waterborne and foodborne transmission; cebiche<br />
From where did V. <strong>cholerae</strong> originate ?
From where did V. <strong>cholerae</strong> originate ?<br />
23 Oct, 24 and 29 Dec 1990<br />
11 December 1990<br />
26 Dec 1990, and 16 Jan 1991<br />
• PIURA (28 Jan 91)<br />
• CHICLAYO<br />
• TRUJILLO<br />
13 January 1991<br />
• CHIMBOTE (24 Jan 91)<br />
• CHANCAY (23 Jan 91)<br />
• LIMA<br />
Seas C. Am J Trop Med Hyg 2000;62:513-7.<br />
Distance from Lima<br />
1050 Km<br />
763 Km<br />
570 Km<br />
440 Km<br />
60 Km
El Niño Current<br />
Humboldt Current
Study case control-CHOLERA CASES<br />
Cayetano Heredia Hospital<br />
(Feb-Mar 1991)<br />
Risk factors<br />
1. Drink water outside the home<br />
2. Consume food from street vendors (chicha, ice cream<br />
fresh cheese)<br />
3. Relative with diarrhea<br />
4. Unemployed people
RISK FACTORS FOR CHOLERA, PERU 1991<br />
Risk factor Cases Controls OR (95%CI)<br />
Drinking unboiled water 62 30 3.8 (1.5-9.8)<br />
59 28 3.1 (1.3-7.3)<br />
Adding ice to beverages 88 63 4.0 (1.0-17)<br />
Drinking on street vendors 56 19 17.0 (2.2-133)<br />
Eating on street vendors 26 5 8.0 (2.2-29)<br />
Eating cool leftover rice 38 22 2.1 (1.1-4.5)<br />
Drinking boiled water 62 92 0.1 (0.02-0.5)<br />
Drinking acidic beverages 52 77 0.4 (0.2-0.7)
ENVIRONMENTAL SPREAD OF CHOLERA IN PERU<br />
Sample V. <strong>cholerae</strong>/dl<br />
Lima<br />
sea water 10 4<br />
river water 10 3<br />
municipal sewage 10 5<br />
finfish (skin, intestines) present<br />
Titicaca lake, Puno 4<br />
River water, Iquitos 10 3<br />
Sea water, Callao 10 4<br />
Tamplin ML, Carrillo CC. Lancet 1991;338:1216-7.
NEW ISSUES IN PREVENTION AND CONTROL<br />
• Detecting V. <strong>cholerae</strong> in the environment:<br />
» detection of V. <strong>cholerae</strong> O1 in the environment<br />
preceded the appearance of cases in the community<br />
by 2-3 months<br />
» detection of V. <strong>cholerae</strong> O1 in the sewage of Lima city<br />
preceded the appearance of cases<br />
• Abundance of V. <strong>cholerae</strong> O1 correlates with the<br />
abundance of copepods. Plankton mass and displacement<br />
can be explored by using satellite images<br />
• The integration of several disciplines including<br />
epidemiology, marine biology, microbiology, medicine, and<br />
satellite imagery may prevent global epidemics
THE CHOLERA EPIDEMIC IN PERU
ACUTE RENAL FAILURE AT CAYETANO HEREDIA<br />
HOSPITAL DURING 1992<br />
incidence rate was 10.6 per 1000 (19,826 studied), higher<br />
among the elderly; 10% vs 1.3%<br />
non-oliguric ARF predominated<br />
59% required dyalisis<br />
mean duration (SD) of hospitalization 11.2 (7.2) days<br />
overall case fatality rate was 18%:<br />
» higher in oliguric ARF; 26% vs 4%, p
CHOLERA IN ESPECIAL POPULATIONS<br />
Cholera in children:<br />
» clinical presentation is similar<br />
» more atypical findings; fever, seizures and coma<br />
» hypokalemia, hyponatremia and hypoglycemia are<br />
more commonly seen compared to adults<br />
Pregnants:<br />
» clinical presentation is similar<br />
» 50% of fetal death during third trimester<br />
Cholera in the elderly:<br />
» high rate of complications<br />
» high mortality rates
PRINCIPLES OF REHYDRATION THERAPY<br />
Rapid replacement of fluid deficits<br />
Correction of metabolic acidosis<br />
Correction of potassium deficits<br />
Replacement of continuous fluid losses
PRACTICAL GUIDELINES FOR THE<br />
TREATMENT OF CHOLERA<br />
1 Evaluate the degree of dehydration on arrival<br />
2 Rehydrate patients in two phases<br />
a rehydration phase: lasts 2-4 hours<br />
b maintenance phase: until diarrhea abates<br />
3 Register output and input in pre-designed charts, and<br />
review the data collected periodically
PRACTICAL GUIDELINES FOR THE<br />
TREATMENT OF CHOLERA<br />
4 Use the IV route only to rehydrate:<br />
a severely dehydrated patients; rate of infusion during<br />
rehydration phase 50-100 ml/Kg/h<br />
b patients with some dehydration not tolerating PO<br />
c high stool purgers (>10 ml/Kg/h) during maintenance<br />
5 Use ORS for all patients during the maintenance phase<br />
at a rate of 800-1000 mL/h, matching ongoing losses<br />
6 Discharge patients only if:<br />
a oral tolerance 1000 ml/h<br />
b urine output 40 ml/h<br />
c stool volume 400 ml/h
ANTIMICROBIALS IN CHOLERA<br />
their use is not lifesaving<br />
effective antimicrobials reduce:<br />
» the volume of stools by half<br />
» the excretion of vibrio<br />
» fluid requirements for rehydration<br />
single dose regimens are preferred<br />
tetracyclines are the first choice, but resistant strains<br />
have emerged recently<br />
erythromycin or quinolones are alternatives against<br />
resistant strains
CHOLERA IN ZAIRE, 1994<br />
• 1.2´Hutus fled Rwanda to Kivu-Zaire during the second<br />
week of July 1994<br />
• 3 days later V. <strong>cholerae</strong> O1, Inaba, El Tor, resistant to<br />
tetracyclines and cmx, was isolated from a patient with<br />
diarrhea<br />
• 32000 cases in approximately one month<br />
• CFR: 8-23%, 50% did not receive therapy<br />
• utility of available vaccines in preventing the spread of<br />
cholera<br />
• the epidemic of cholera was followed by an epidemic of<br />
multiresistant S. dysenteriae type 1
CHOLERA IN CONGO
COUNTRIES WHERE V. <strong>cholerae</strong> O139 CASES<br />
HAVE BEEN DETECTED<br />
Countries 1993 1994 1995 1996 1997 1998<br />
Bangladesh + + +<br />
China + +<br />
India + + + +<br />
Indonesia +<br />
Malaysia + +<br />
Myanmar + +<br />
Nepal + +<br />
Pakistan +<br />
Sri Lanka +<br />
Thailand + +
CHOLERA. PREVENTION AND CONTROL<br />
Early case-finding<br />
Establishing treatment centers<br />
Treatment of cases<br />
Epidemiological investigations<br />
Laboratory support<br />
Health education<br />
Water supply and food safety<br />
Sanitation<br />
Restriction of trade and travel
Cholera 1991<br />
THIS PANDEMIC COULD PRODUCE 3-4<br />
MILLION CASES WITH A MORTALITY OF<br />
30,000 IN LATIN AMERICA<br />
Carlyle Guerra De Macedo (PAHO)
THE CHOLERA EPIDEMIC IN PERU<br />
Incidence x 100,000<br />
100<br />
80<br />
60<br />
40<br />
20<br />
0<br />
TOTAL NUMBER OF CASES/CUMULATIVE<br />
INCIDENCE RATES (X 100,000)<br />
1991 322,562/1434<br />
1992 239,139/1066<br />
1993 62,366/278<br />
1994 23,887/106<br />
1995 15,628/69<br />
1991 1992 1993 1994 1995
Number of cases x 1000<br />
CHOLERA IN THE AMERICAS: NUMBER OF<br />
NOTIFIED CASES, AND CASE FATALITY RATE<br />
1991-2005<br />
500<br />
400<br />
300<br />
200<br />
100<br />
0<br />
1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005<br />
Number of cases Case fatality rate (%)<br />
2<br />
1.5<br />
1<br />
0.5<br />
0<br />
Case fatality rate (%)
NUMBER OF CASES AND NUMBER OF<br />
COUNTRIES REPORTING CHOLERA, 1990-2005<br />
Number of cases x 1000<br />
800<br />
700<br />
600<br />
500<br />
400<br />
300<br />
200<br />
100<br />
0<br />
1990 1991 1992 1993 1994 1995 1996 1997 1998 1999 2000 2001 2002 2003 2004 2005<br />
Number of cases Number of countries<br />
Weekly Epidemiological Record 2006;81:297-308.<br />
100<br />
90<br />
80<br />
70<br />
60<br />
50<br />
40<br />
30<br />
20<br />
10<br />
0<br />
Number of countries
CHOLERA AMONG TRAVELERS<br />
Taylor D. et.al. CID 1996;22:1109-10.<br />
Travelers from/to Year Incidence (x100,000)<br />
USA/Asia 1960-80 0.17<br />
Western nations/Asia 1991 0.05<br />
Western nations/Ecuador 1991 0.30<br />
Japan/Bali 1991 13.0<br />
USA embassy employees 1991-3<br />
all employees 30.0<br />
U.S. citizens 44.0<br />
Peruvian citizens in Lima 136.0
HOST RISK FACTORS<br />
Age<br />
Malnutrition<br />
Pregnancy<br />
Breast feeding<br />
O blood group<br />
Infection by Helycobacter pylori*<br />
Other conditions that reduce gastric acidity<br />
* León-Barúa R. Trans R Soc Trop Med Hyg. 2006;100:567-72
ROLE OF O BLOOD GROUP<br />
• Hospitalized patients with cholera were most likely to<br />
be of O blood group than controls<br />
• Volunteers carrying the O blood group presented<br />
more severe diarrhea when challenged with V.<br />
<strong>cholerae</strong> O1<br />
• In a study conducted in Lima; people with O blood<br />
group had almost 5 times higher risk to acquire<br />
severe cholera than people with other blood groups:<br />
( RR 4.8, 95%CI 2.2-10.7)<br />
• The underlying mechanism is not clearly understood
IMPACT OF THE CHOLERA EPIDEMIC<br />
• effect of El Niño during 1991<br />
• reduction in trade, commerce and tourism<br />
» reduction in exportation of fish and shellfish<br />
» reduction in exportation of all agricultural products<br />
» severe reduction of tourism<br />
• positive impact<br />
» international cooperation<br />
» investment in sanitation and water supply
Positive aspects of cholera epidemic<br />
• Investment in environmental sanitation<br />
• Application of medical and public health knowledge to<br />
control<br />
• Reduction >30% in children mortality<br />
• A notable reduction in Typhoid fever
T.F.: Impact of cholera in Peru
CHOLERA IN THE WORLD: 1996-2005<br />
Cholera during 1996-2005 is almost confined to Africa:<br />
» 95% 95%<br />
of the world cases in 2005 are reported from Africa<br />
» 31 African countries are reporting cases in 2005<br />
» continuing epidemics in Ghana, Guinea-Bissau, Mauritania<br />
and Senegal<br />
» uneven distribution of CFR: 18% in Guinea to 0.22 in South Africa<br />
» trend toward reduction in CFR over the last 7-8 years<br />
Marked reduction in the number of cases and CFR from<br />
Asia and Latin America<br />
Weekly Epidemiological Record 2006;81:297-308.
NEW ISSUES IN PREVENTION AND CONTROL<br />
Detecting V. <strong>cholerae</strong> in the environment:<br />
» detection of V. <strong>cholerae</strong> O1 in the environment preceded the<br />
appearance of cases in the community by 2-3 months<br />
» detection of V. <strong>cholerae</strong> O1 in the sewage of Lima city<br />
preceded the appearance of cases<br />
Abundance of V. <strong>cholerae</strong> O1 correlates with the<br />
abundance of copepods. Plankton mass and displacement<br />
can be explored by using satellite images<br />
The integration of several disciplines including<br />
epidemiology, marine biology, microbiology, medicine, and<br />
satellite imagery may prevent global epidemics
Cholera slides from Bangladesh<br />
• 1. Epidemiology: 4 years of surveillance 4 different areas of Bangladesh<br />
in<br />
• 2 Predicting outbreaks from environmental assays<br />
• 3. Zoolplankton with V. <strong>cholerae</strong><br />
• 4. Phytoplankton with V. <strong>cholerae</strong><br />
• 5. Satellite imaging.of Bangladesh and Bay of<br />
Bengal, during no epidemics epidemic.<br />
and during large
In October 2010, epidemic cholera broke out in<br />
Haiti<br />
• Cholera had not been reported in Haiti for more than a century 1<br />
• Disease spread rapidly in the absence of natural immunity,<br />
clean water, and proper sanitation 2<br />
Deaths<br />
(n)<br />
140<br />
120<br />
100<br />
80<br />
60<br />
40<br />
20<br />
0<br />
Total deaths, Haiti, 20 October 2010–4 April 2011 3<br />
20/10/10<br />
27/10/10<br />
03/11/10<br />
10/11/10<br />
17/11/10<br />
24/11/10<br />
01/12/10<br />
08/12/10<br />
15/12/10<br />
22/12/10<br />
29/12/10<br />
05/01/11<br />
12/01/11<br />
19/01/11<br />
26/01/11<br />
02/02/11<br />
09/02/11<br />
16/02/11<br />
23/02/11<br />
02/03/11<br />
09/03/11<br />
16/03/11<br />
23/03/11<br />
30/03/11<br />
Week beginning<br />
Since the 1st laboratory-confirmed case report of cholera was made on<br />
19 October 2010, cholera has killed >4500 people in Haiti 3<br />
1. Chin C-S et al. N Engl J Med 2011;364:33-42; 2. Cyranoski D. Nature 2011;469:273-4;<br />
3. PAHO. Available at http://new.paho.org/blogs/haiti/?p=1959
ien ha echado el Vibrio <strong>cholerae</strong> en el rio Artibonite?<br />
Agua potable:un lujo mas que un derech
The cholera epidemic has not been contained<br />
within Haiti<br />
• Since the beginning of the outbreak in Haiti, imported<br />
cases have been notified in various countries, including<br />
the Dominican Republic<br />
» The 1st laboratory-confirmed case was reported in the<br />
Dominican Republic on 16 November 2010 1<br />
» In the same week, the US reported an imported case<br />
in a patient from Florida 1<br />
» Up to 26 February 2011, there were 568 laboratorylaboratoryconfirmed cases and 6 deaths in the Dominican Republic 2<br />
1. PAHO. Epidemiological Alert (23 November 2010). Available at: http://new.paho.org/hq/index.php?<br />
option=com_content&tak=view&id+1239&Itemid=1091&lang=en;<br />
2. PAHO. Epidemiological Alert (February 8 to 26, 2011). Available at:<br />
http://new.paho.org/hq/index.php?option=com_content&task=view&id=5153&Itemid=2206
analysis<br />
demonstrate<br />
s close<br />
identity<br />
between<br />
Haitian and<br />
South Asian<br />
El Tor O1<br />
cholera<br />
strain<br />
Cholera was most likely imported to Haiti by<br />
visitors from South Asia<br />
The Haitian<br />
strains do<br />
not resemble<br />
Latin<br />
American<br />
cholera or<br />
Chin C-S et al. N Engl J Med 2011;364:33-42<br />
strains
Polluted water is the most common source of<br />
cholera transmission<br />
Life cycle of V. <strong>cholerae</strong><br />
Large<br />
volumes of<br />
hyperinfective<br />
V. <strong>cholerae</strong><br />
3<br />
4<br />
Poor sanitation<br />
Poor people are more vulnerable<br />
to infection with V. <strong>cholerae</strong><br />
Discharge in the environment<br />
5<br />
Epidemic<br />
spread of<br />
cholera<br />
Free-swimming<br />
V. <strong>cholerae</strong><br />
Non O1,<br />
O139<br />
Genetic<br />
exchanges<br />
O1, O139<br />
2<br />
1<br />
V. <strong>cholerae</strong> attached to<br />
aquatic life forms<br />
Contaminated<br />
food and water
Contact with freshly shed V. <strong>cholerae</strong> is much<br />
more likely to cause disease<br />
Transmission via contaminated<br />
water (higher ID 50 ) accounts for<br />
slower dynamics<br />
Transmission through contact with<br />
fresh feces or vomit (lower ID 50 )<br />
causes explosive epidemics
Crowding and poor sanitation exacerbate<br />
cholera transmission<br />
Cholera is transmited<br />
vi a<br />
t h e f ec al –or al r out e,<br />
with epidemics often<br />
ocuring after war,<br />
civil unrest, and natural<br />
disasters, when water or<br />
fod suplies become<br />
c ont ami nat ed wi t h<br />
V . c h ol er ae, compounded<br />
by crowded living<br />
conditions with<br />
l i mi t ed s ani t at i on<br />
Zuckerman JN et al. Lancet Infect Dis 2007;7:521-30
A multiple approach is critical for effective and<br />
sustainable cholera control<br />
• Safe water<br />
• Food safety<br />
Remain as longterm<br />
preventive<br />
• Sanitation<br />
measures<br />
• Health<br />
Fast-acting education supplementary measure:<br />
implementation of vaccination<br />
WHO. Weekly epidemiological record 2010;85:117-28. Available at: http://www.who.int/wer/2010/wer8513.pdf
Vaccine against cholera:<br />
easy administration, no needle, no pain<br />
Dukoral<br />
• Licensed in 60 countries (first licensed in<br />
1991)<br />
• High acceptance<br />
• Excellent tolerability<br />
• Local intestinal and systemic immunity,<br />
providing herd protection<br />
• Prequalified by the WHO for United Nations<br />
purchase<br />
• Previous use during complex emergencies in<br />
Indonesia, Sudan and Uganda, as well as in<br />
the urban slums of Mozambique<br />
Waldor MK et al. N Engl J Med 2010; 363:2279-2282
Reactive mass vaccination can prevent cholera<br />
cases and deaths<br />
The number of cases that would have been prevented during the 2008-2009 outbreak in<br />
Zimbabwe using the currently licensed 2-dose oral cholera vaccine<br />
Total<br />
cholera<br />
cases<br />
Attac<br />
k<br />
rate/<br />
1000<br />
Rapid<br />
response a<br />
Total number (%) of<br />
cholera cases prevented<br />
(50% vaccine coverage)<br />
Delayed<br />
response b<br />
Maximum<br />
delay c<br />
Rapid<br />
response a<br />
Total number (%) of<br />
cholera cases prevented<br />
(75% vaccine coverage)<br />
Delayed<br />
response b<br />
Maximum<br />
delay c<br />
98,591 7.39 34,900 (40) 12,789(13) 474 (0) 59,100 (60) 19,183 (19) 711 (1)<br />
Population 13,349,000, outbreak duration 54 weeks<br />
A rapid response with 50% vaccination coverage could have prevented<br />
34,900 (40%) cholera cases and 1,695 (40%) deaths<br />
a 10 weeks between 1st reported case and total community immunization;<br />
b 21 weeks between 1st reported case and total community immunization;<br />
c 33 weeks between 1st reported case and total community immunization<br />
Reyburn R et al. PLoS Negl Trop Dis 2011;5:e952
Is the need to choose between options for cholera<br />
control in Haiti still reasonable?<br />
Improvements in provision of clean water and sanitation have not been<br />
sufficient so far, in Haiti or elsewhere 1,2<br />
Maintaining provision of clean water and sanitation can be difficult 3<br />
The incidence of new cases may increase with the upcoming rainy<br />
season 4<br />
Endemic cholera may persist in Haiti at the end of the current epidemic,<br />
with continued intermittent outbreaks generating more cases and deaths<br />
than previously estimated 3,5<br />
Averting even a modest number of cases will save lives 6<br />
However, large scale cholera vaccination remains<br />
difficult to implement due to limited vaccine<br />
supply 1-6<br />
1. Ryan ET. PLoS Negl Trop Dis 2011; 5(1): e1003;<br />
2. Waldor MK et al. N Engl J Med 2010; 363:2279-2282;<br />
3.Sack DA. Lancet 2011; 377:1214-1216<br />
4.Andrews JP and Basu S. Lancet 2011; 377:1248-1255;<br />
5. Chao DL et al. Proc Natl Acad Sci USA 2011;108:7081-7085;<br />
6. Tuite AR et al. Ann Intern Med 2011;Mar 7 [Epub ahead of print]
Ministerio de Salud<br />
Dirección General de Epidemiología<br />
Situación Actual del Cólera en Haití<br />
al 17 de abril del 2011<br />
Departamentos Población<br />
Desplazados<br />
15%<br />
Artibonite 1299398 162509<br />
Central 581505 90997<br />
Grande anse 363377 119871<br />
Nippes 263551 33351<br />
North 823043 13531<br />
North Est 309918 8500<br />
Nord Ouest 531198 45862<br />
Ouest 3096967 660885<br />
Sud 621651 88533<br />
Sud est 484675 32253<br />
Total 8375283 1256292<br />
Desplazados: Post terremoto 12 de enero 2010
Summary<br />
• Epidemic cholera broke out in Haiti in October 2010,<br />
with >4500 deaths to date<br />
• Cholera was most likely imported to Haiti from South Asia by human<br />
activity<br />
• Cholera follows a fecal–oral route of transmission,<br />
is characterized by acute profuse watery diarrhea,<br />
and can kill the patient within a day<br />
• WHO recommends reactive oral cholera vaccines alongside<br />
treatment, provision of clean water, and improved sanitation to<br />
control endemic and epidemic cholera<br />
• Large-scale vaccination in Haiti is difficult to implement due to<br />
limited vaccine supply, as well as potential for relaxation of<br />
sanitation and diversion of other healthcare resources, but would<br />
save a substantial number of lives
Pre-emptive and reactive cholera vaccination are<br />
recommended by WHO for outbreak control<br />
• Pre-emptive vaccination should be used to prevent potential<br />
outbreaks and contain actual outbreaks,<br />
targeting at-risk groups<br />
» During complex emergencies that compromise water<br />
and sanitation<br />
» When neighboring regions experience an outbreak<br />
» When disease incidence increases in an endemic region<br />
• Reactive vaccination should be considered, depending on local<br />
factors<br />
• Vaccination for outbreak control must achieve<br />
high population coverage<br />
• Vaccination should be in conjunction with treatment, provision of<br />
clean water, and improved sanitation<br />
WHO. Weekly epidemiological record 2010;85:117-28. Available at: http://www.who.int/wer/2010/wer8513.pdf
NEW ISSUES IN PREVENTION AND CONTROL<br />
• Detecting V. <strong>cholerae</strong> in the environment:<br />
» detection of V. <strong>cholerae</strong> O1 in the environment<br />
preceded the appearance of cases in the community<br />
by 2-3 months<br />
» detection of V. <strong>cholerae</strong> O1 in the sewage of Lima city<br />
preceded the appearance of cases<br />
• Abundance of V. <strong>cholerae</strong> O1 correlates with the<br />
abundance of copepods. Plankton mass and displacement<br />
can be explored by using satellite images<br />
• The integration of several disciplines including<br />
epidemiology, marine biology, microbiology, medicine, and<br />
satellite imagery may prevent global epidemics
CHANGING PATTERNS IN<br />
CHOLERA EPIDEMICS<br />
Cholera is still a major public health problem in<br />
developing countries<br />
Changes in the agent, the environment, and the host<br />
promote cholera transmission<br />
The implementation of effective and timely emergency<br />
preparedness programs is urgently needed<br />
Predicting future epidemics will require multidisciplinary<br />
work
“ The scientific community and world<br />
leaders must therefore work together<br />
to use knowledge and its applications<br />
to improve the conditions of the<br />
planet. The connection between<br />
cholera and the environment provides<br />
a paradigm for this perspective”<br />
Colwell RR. Intern Microbiol 2004;7:285-9.
“ From the time the cholera<br />
proclamation was issued, the local<br />
garrison shot a cannon from the<br />
fortress every quarter hour, day and<br />
night, in accordance with the local<br />
superstition that gun powder purified<br />
the atmosphere”<br />
Gabriel García Márquez. Love in the time of cholera