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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

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