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University of Khartoum Faculty of Medicine Department of Community Medicine

Cholera

Amal Ar. Osman

OUTLINES

EPIDIMIOLOGYHISTORICAL BACKGROUND CAUSE TRANSMISSION DISTRIBUTIONCLINICAL MANIFESTATIONLABROTATY INVESTIGATIONMANGMENT PREVENTION AND CONTROL

Death moved continually about the ranks of the army, not the death they had been trained to meet unflinchinglybut a silent , unnoticed , almost ignominious summons, scarcely less sudden and far more painful than the bullet or the sword cutSIR WINSTON CHURCHIL 1899

Definition

Cholera is an acute intestinal infection caused by ingestion of food or water contaminated with the bacterium Vibrio cholerae.Every year, there are an estimated 35 million cholera cases and 100 000120 000 deaths due to cholera. The short incubation period of two hours to five days, enhances the potentially explosive pattern of outbreaks.

Historical background

The condition of dehydratingdiarrhoea was mentioned around the time of Hippocrates (460-377 BC)

V. cholerae has caused seven worldwide disease outbreaks or pandemics since 1817, killing millions of people and infecting millions more.

Cholera is now endemic in many countries

Prior to 1850, it was thought that cholera was caused by breathing in bad air - miasma and that protection was offered by strong smelling substances such as herbs and camphor.

Deaths in India between 1817 and 1860, in the first three pandemics of the nineteenth century, are estimated to have exceeded 15million people. Another 23million died between 1865 and 1917, during the next three pandemics. Cholera deaths in the Russian Empire during a similar time period exceeded 2million

18161826: The first cholera pandemic, began in Bengal, and then spread across India into china and Indonesia 18291851: A second cholera pandemic reached Russia ,Hungary and Germany; it killed 150,000 people in Egypt that year. it reached London and the United Kingdom (where more than 55,000 people died) and Paris 20,000 died (of a population of 650,000)The epidemic reached Quebec, Ontario, Nova Scotia and New York in the same year, and the Pacific coast of North America by 1834Over 15,000 people died of cholera in Mecca in 1846

18521860: The third cholera pandemic mainly affected Russia, with over one million deathsIt also spread in south east Asia , Chicago , London ( ended after john snow discovered the water source) , Venezuela and brazil

18631875: The fourth cholera pandemic spread mostly in Europe and Africa. At least 30,000 of the 90,000 Mecca pilgrims died from the disease. 18811896: The fifth cholera pandemic, the epidemic cost 250,000 lives in Europe and at least 50,000 in the Americas

8991923: The sixth cholera pandemic had little effect in western Europe because of advances in public health, but major Russian cities and the Ottoman Empire were particularly hard hit by cholera deaths9611975: The seventh cholera pandemic began in Indonesia reached Bangladesh ,India ,soviet union and Japan

historyCholera outbreaks in sudan

The first medical service in Sudan was established by Turku-Egyptians after 1820was rudimentary and geared the military machines and its knowledge of the most serious diseases was limited.During the last century the classical cholera was areal menace to the Sudan and the several epidemics which hit the country were not uncommonly heralded by severe famines

A series of major cholera outbreak recurred successively over practically every decade of the century after the second pandemicThe epidemic cycles of the cholera which devastated the land and caused unprecedented concern ,came either across the red sea from Arabia or crept up the Nile from Egypt The disease presented grave problems in an environment which lacked doctors and medical equipment and its periodic onslaughts resulted in a frightful mortality rate.

The Sudan faced more than 7 epidemics of cholera during the ninetieth century several of them were associated with drought and famine 1831 was brought by pilgrims returning from Mecca through Egypt1835-1837 cholera displayed great activity in Egypt , the Sudan and Ethiopia 1849 by Mecca pilgrims and the ship traffic across the red sea 1857 from Egypt 1865 the infection was carried across the red sea from Jeddah to Suakin and Massawa and penetrated from there into heartland of Sudan and Ethiopia 1872 via Mecca across the red sea 1889-1890 after Abyssinian war (Mahadist against king john of Ethiopia) the epidemic extended over the whole of the Sudan and ran along the banks of the river Nile as far as Egypt1896 creep up the Nile from Cairo down to Sudan

During the last century classical cholera was not detected in Sudan ; the vigorous enforcement of the international sanitary regulations under the British medical administration was a major factor in ending a century of tragic experience with this much dreaded disease.

2009

Causative Organism

Vibrio consists of Gram-negative rods, motile by means of a single polar flagellum. Vibrios are capable of both respiratory and fermentative metabolism. O2 is a universal electron acceptor

Most vibrios have relatively simple growth factor requirements and will grow in synthetic media with glucose as a sole source of carbon and energy. However, since vibrios are typically marine organisms, most species require 2-3% NaCl or a sea water base for optimal growth.

Vibrios are one of the most common organisms in surface waters of the world. They occur in both marine and freshwater habitats and in associations with aquatic animals.

V. cholerae and V. parahaemolyticus are pathogens of humans. Both produce diarrhea, but in ways that are entirely different. V. parahaemolyticus is an invasive organism affecting primarily the colon; V. cholerae is noninvasive, affecting the small intestine through secretion of an enterotoxin. Vibrio vulnificus is an emerging pathogen of humans. This organism causes wound infections, gastroenteritis, or a syndrome known as "primary septicemia

Vibrio cholerae

V.Cholerae are killed within 30 mins. by heating at 56deg c or within few seconds by boiling . They remain in ice for 4-6 days or longer .Drying and sunshine will kill them in few hours , while coal tar disinfectant can easily destroy themElTor tends to be more resistant than classical biotype

There are two serogroups of V. cholerae O1 and O139 cause outbreaks. V. cholerae O1 causes the majority of outbreaks, while O139 is confined to South-East Asia. Non-O1 and non-O139 V. cholerae can cause mild diarrhea but do not generate epidemics.

Recently, new variant strains have been detected in several parts of Asia and Africa. Observations suggest that these strains cause more severe cholera with higher case fatality rates

In any single epidemic , one particular serogroup or biotype tends to be dominant, but serotype switching is commonly seen in cholera epidemics worldwide and is thought to be driven by the development of population immunity to the circulating serotype

El Tor vibrios may be distinguished from the classical vibrios by the following tests : ElTor vibrios agglutinate chicken and sheep erythrocytesThey are resistant to classical phage IVThe VP reaction and haemolytic tests do not give consistent results

Epidemiologically , cholera due to EL Tor biotype differs from the classical in the followingHigher incidence of mild and asymptomatic infections Fewer secondary cases Chronic carriers The organism survives more in the extra intestinal environment

transmission

Reservoir

Include both human and environmentHuman could be 1-case or 2-carrier75% of patients doesnt develop any symptoms and remain infective for 7-14 days Carriers are usually temporal and rarely chronic

Cholera transmission is closely linked to inadequate environmental management. Transmission occurs from man to man via fecally contaminated water Contaminated food and drinks Direct contact secondary transmission)

Bottle feeding could be a significant risk factor for infants Fruit and vegetables washed with contaminated water could be a source of infectionCooked food may be contaminated by handling or flies

Cholera remains a global threat to public health and a key indicator of lack of social development

Incubation periodFrom few hours up to 5 days , Commonly 1-2 days

Infective dose Cholera is a dose related disease .Infection occurs when the number of vibrios ingested exceed that infective for a particular individualExpermintal work suggest that a very high dose in a normal person 10)11 organism is required for producing clinical disease

pathophysiology

V. cholerae cells enter the bodyand make their way through the digestive system.Approximately two-thirds survive the acidic conditions of the stomach; survivors conserve energyuntil they enter the small intestine where they begin production of their flagella

The flagellum propels each Vibrio cell forward through the mucus layer to theintestinal wall. V. cholerae also produces enzymes that digest the layers of mucus, which helps with access to the epithelial cells lining the intestine, as well as detachment from cells that are beinglost due to the bodys defense mechanisms.

Then it start production of hairlike appendages called frimbriae or pili which are formed on the bacterial cell surface. These structures are made of protein and allow the bacteria to attach to the lining of the intestine.Growth: For symptoms to persist, the bacteria must continue to multiply in the intestine.

in the intestine, the bacteria invade the host cell. Production of CT is the final stage in pathogenesis.

cAMP causes increase in the fluid excretion but not increase perstalsis46

Host factors

Attack rate is higher in children Gastric acidityImmunityavailability of surface receptors for CT on the host cell surface Blood group O

Environmental factors Contaminated water and food

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immunology

Protective immunity in those exposed to cholera is induced almost exclusively by antibodies producedin the intestine. These antibodies prevent bacterial colonisation and multiplication, and they inactivatethe CT. Immunoglobulins IgA, IgG and IgM have all been detected, although IgA is the most important.

The antibodies prevent the CT from binding with receptors on the cell surface. Natural immunity is provided by IgM followed by a switch to IgG. There is a 3- year period post infection where patientsremain immune to cholera as a result of acquired, natural immunity.

In areas where cholera is endemic such as Bangladesh, infection rates are low among adults whencompared to the children in the same area, whereas in areas where new epidemics arise rates are higherin the adult population. This discrepancy illustrates a resistance linked to the presence of circulatingvibriocidal antibodies to cholera.

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Clinical manifestations

The severity of the disease depends on the rapidity and duration of fluid loss

90% of ElTor cases are mild and clinically indistinguishable from other acute diarrheas

Typical case of cholera shows 3 stages : stage of evacuation Stage of collapse Stage of recovery

An acute bacterial enteric disease characterized in its severe form by sudden onset ,profuse, painless , effortless watery diarrhea Nausea and profuse vomiting occur early in the course of illness

Watery diarrhea

Complications

Rapid dehydration Acidosis Circulatory collapse Hypoglycemia in children Renal failure Electrolyte imbalance (Na ,Ca)In severely dehydrated cases (cholera gravis ) death occurs within few hours and case fatality rate is up to 50%

Diagnosis

Collection of stool: By rubber catherter Rectal swab

For clinical purposes a quick presumptive diagnosis can be made by dark field or phase microscopic visualization of vibrios in stool moving like shooting stars inhibited by preservative free serotype specific anti serum

The etiology is confirmed by isolation if v.cholerae serogroups from a stool specimenIdeally the isolated serogroup should be tested for cholera toxin production or cholera toxin gene sequences (ctxA)Strains that dont possess cholera toxin can lead to acute watery diarrhea but not causing cholera or epidemic

One step dipstick tests for rapid antigen detection of V.cholerae O1 and O139 are available and has shown promise in initial field evaluation : however these tests do not yield isolates for subtypes or antimicrobial resistance .

In epidemics , once laboratory confirmation and antibiotic susceptibility have been established its is un necessary to confirm all subsequent cases . A shift should be made to the primary use of WHO clinical case definition of cholera surveillance as follows :

Disease unknown in area : severe dehydration or death from acute watery diarrhea in a patient aged 5 years or older Endemic cholera : acute watery diarrhea with or without vomiting in patient aged 5 years or older Epidemic cholera : acute watery diarrhea with or without vomiting in any patient

Prolonged outbreak should include periodic lab confirmation and anti microbial susceptibility testing of small proportion of cases to monitor for anti microbial resistance

Treatment

Treatment

Cholera is an easily treatable disease. Up to 80% of people can be treated successfully through prompt administration of oral rehydration salts (WHO/UNICEF ORS standard sachet)

Very severely dehydrated patients require administration of intravenous fluids. & appropriate antibiotics to diminish the duration of diarrhea, reduce the volume of rehydration fluids needed, and shorten the duration of V. cholerae excretion

In order to ensure timely access to treatment, cholera treatment centers (CTCs) should be set up among the affected populations.With proper treatment, the case fatality rate should remain below 1%.

Mass administration of antibiotics is not recommended, as it has no effect on the spread of cholera and contributes to increasing antimicrobial resistance.

Steps for successful treatmentAssessment of dehydrationRehydrationReassessment of fluid imbalanceAntibiotic treatmentAvoid/managing complicationsZinc for under fiveWhen to dischargeConsider other conditionsCourtesy of Dr. Ahmed Elamin FMOH-Epidmology department

Assessment of dehydrationAt triage stationCourtesy of Dr. Ahmed Elamin FMOH-Epidmiology department

Ask about:No dehydrationSome dehydrationSevere dehydrationDiarrhea < 4 /day4 to 10 motion> 10 episodeVomitingrareSometimesFrequentThirstNone Drinks eagerly and/ or isThirstyUnable to drinkUrine Normal amount Small in amount and yellowishNo urine for > 6 hours

Courtesy of Dr. Ahmed Elamin FMOH-Epidmiology department

Observe the:No dehydrationSome dehydrationSevere dehydrationGeneral conditionWell/ alertRestless/ irritable Lethargic/ unconsciousEyesNormal Sunken Very sunkenbreathingnormalFaster than normalVery fast and deepAnterior fontanel Normal Sunken Very sunken

Courtesy of Dr. Ahmed Elamin FMOH-Epidmiology department

Examine the:No dehydrationSome dehydrationSevere dehydrationSkin pinchGoes back quicklyGoes back slowly(2 seconds)Goes back very slowly(3 seconds)Radial pulse Full volumeLow volume Weak/absent

Courtesy of Dr. Ahmed Elamin FMOH-Epidmiology department

Treatment of some dehydrationAgeWeight (kg)Amount of ORS in firstFOUR* or SIX* hours (ml)